18 results on '"Meichun Hu"'
Search Results
2. Identification of a luminescent platinum(II) complex with BODIPY derivative as novel photodynamic therapy agent for triple negative breast cancer cells
- Author
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Yujing Wang, Shuping Wang, Qingqing Wang, Wanyu Tang, Li Lin, Tao Zhang, Meichun Hu, and Xiaobo Wang
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Inorganic Chemistry ,Biochemistry - Published
- 2023
3. Isobavachalcone Attenuates NLRP3 Inflammasome-related Pyroptosis and Induces Apoptosis via Arresting Cell Cycle in Glioblastoma
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Yueshan Wu, Jing Chang, Juanjuan Ge, Kangyan Xu, Quan Zhou, Xiaowen Zhang, Ni Zhu, and Meichun Hu
- Abstract
Glioblastoma (GBM) is the worst and most common malignant intracranial tumor with high mortality rates and almost invariably poor prognosis even after surgery, radiotherapy, chemotherapy and emerging immunotherapies. Therefore, it is important to find new therapeutic drugs for GBM treatment. In the present study, we aimed to explore the effect of one natural chalcone—Isobavachalcone (IBC) on GBM and clarify its anti-cancer mechanisms. It was observed that IBC could inhibit GBM cell proliferation, migration and invasion in vitro and prevent tumor growth without any significant drug toxicity in vivo. Mechanistically, IBC may target NOD-like receptor family pyrin domain-containing 3 (NLRP3) transcription factor estrogen receptor 1 (ESR1) by network pharmacology and molecular docking analysis. Experimentally, IBC reduced NLRP3 inflammasome-related pyroptosis and inflammation, arrested cell cycle at G1 phase, and induced mitochondria-dependent apoptosis in GBM cells. These results indicated that IBC is a potential therapeutic drug against GBM and provide a new insight into GBM treatment.
- Published
- 2022
4. Isobavachalcone's Alleviation of Pyroptosis Contributes to Enhanced Apoptosis in Glioblastoma: Possible Involvement of NLRP3
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Yueshan Wu, Jing Chang, Juanjuan Ge, Kangyan Xu, Quan Zhou, Xiaowen Zhang, Ni Zhu, and Meichun Hu
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Molecular Docking Simulation ,Cellular and Molecular Neuroscience ,Chalcones ,Neurology ,Inflammasomes ,NLR Family, Pyrin Domain-Containing 3 Protein ,Neuroscience (miscellaneous) ,Estrogen Receptor alpha ,Pyroptosis ,Humans ,Apoptosis ,Glioblastoma ,Transcription Factors - Abstract
Glioblastoma multiforme (GBM) is the most malignant intracranial tumor with high mortality rates and invariably poor prognosis due to its limited clinical treatments. There is an urgent need to develop new therapeutic drugs for GBM treatment. As a natural prenylated chalcone compound, Isobavachalcone (IBC)'s favorable pharmacological activities have been widely revealed. However, potential inhibitory effects of IBC on GBM have not been explored. In the present study, we aimed to detect the effects of IBC on GBM and clarify its anti-GBM mechanisms for the first time. It was observed that IBC could inhibit GBM cell proliferation, migration, and invasion in vitro and prevent tumor growth without any significant drug toxicity in both subcutaneous and orthotopic GBM xenograft tumor models in vivo. Mechanistically, IBC may target NOD-like receptor family pyrin domain-containing 3 (NLRP3) transcription factor estrogen receptor α (ESR1 gene) by network pharmacology and molecular docking analysis. Experimentally, IBC alleviated NLRP3 inflammasome-related pyroptosis and inflammation, arrested cell cycle at G1 phase, and induced mitochondria-dependent apoptosis in GBM cells. IBC's inhibition on NLRP3 could be rescued by the NLRP3 antagonist CY-09 both in vitro and in vivo. These results indicate that IBC is a potential therapeutic drug against GBM and provide a new insight into GBM treatment.
- Published
- 2022
5. Numerical simulation of coupling characteristics of optical fiber with a rectangular hole
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Libo Yuan, Meichun Hu, Ai Zhou, Jianxia Liu, and Min Tang
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Optical fiber ,Materials science ,Physics::Optics ,02 engineering and technology ,01 natural sciences ,law.invention ,010309 optics ,020210 optoelectronics & photonics ,Optics ,Beam propagation method ,law ,0103 physical sciences ,0202 electrical engineering, electronic engineering, information engineering ,Fiber ,Electrical and Electronic Engineering ,Instrumentation ,business.industry ,High-refractive-index polymer ,Atomic and Molecular Physics, and Optics ,Electronic, Optical and Magnetic Materials ,Coupling (electronics) ,Core (optical fiber) ,Light intensity ,Control and Systems Engineering ,business ,Refractive index - Abstract
The optical fiber with a rectangular hole is proposed. The coupling characteristics of the optical fiber are analyzed and discussed using beam propagation method (BPM). Firstly, the coupling light intensity of the rectangular hole is analyzed. Secondly, the power conversion between the fiber core and the rectangular hole and the periodicity of the power conversion are discussed in detail, respectively. Finally, we study the sensing response of the optical fiber to the surrounding refractive index. The results show that the coupling efficiency are stronger in n rec > n core than in n rec ⩽ n core from the fiber core to the rectangular hole and can reach nearly 50%. The properties are benefited in realizing the surrounding sensing of a high refractive index and increasing the sensing sensitivity of the sensor. Furthermore, the research results also indicate that the compound modes are produced and transmitted in the area between the fiber core and the rectangular hole. Then, they will be converted into fiber modes when the light power is coupled from the rectangular hole to the fiber core. Therefore, The proposed optical fiber has the potential application value in high refractive index sensors and mode converters.
- Published
- 2019
6. Recent advances of enterovirus 71 $$3{\rm C}^{{\rm pro}}$$ targeting Inhibitors
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Kanghong Hu, Rominah Onintsoa Diarimalala, Meichun Hu, and Yanhong Wei
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0301 basic medicine ,Acute flaccid paralysis ,030106 microbiology ,Order (ring theory) ,Biology ,medicine.disease ,Virology ,Hand-foot-and-mouth disease ,Brain stem encephalitis ,Combinatorics ,03 medical and health sciences ,030104 developmental biology ,Infectious Diseases ,medicine ,Mild disease - Abstract
With CA16, enterovirus-71 is the causative agent of hand foot and mouth disease (HFMD) which occurs mostly in children under 5 years-old and responsible of several outbreaks since a decade. Most of the time, HFMD is a mild disease but can progress to severe complications such as meningitis, brain stem encephalitis, acute flaccid paralysis (AFP) and even death; EV71 has been identified in all severe cases. Therefore, it is actually one of the most public health issues that threatens children’s life. $$3{\rm C}^{{\rm pro}}$$ 3 C pro is a protease which plays important functions in EV71 infection. To date, a lot of $$3{\rm C}^{{\rm pro}}$$ 3 C pro inhibitors have been tested but none of them has been approved yet. Therefore, a drug screening is still an utmost importance in order to treat and/or prevent EV71 infections. This work highlights the EV71 life cycle, $$3{\rm C}^{{\rm pro}}$$ 3 C pro functions and $$3{\rm C}^{{\rm pro}}$$ 3 C pro inhibitors recently screened. It permits to well understand all mechanisms about $$3{\rm C}^{{\rm pro}}$$ 3 C pro and consequently allow further development of drugs targeting $$3{\rm C}^{{\rm pro}}$$ 3 C pro . Thus, this review is helpful for screening of more new $$3{\rm C}^{{\rm pro}}$$ 3 C pro inhibitors or for designing analogues of well known $$3{\rm C}^{{\rm pro}}$$ 3 C pro inhibitors in order to improve its antiviral activity.
- Published
- 2020
7. Recent advances of enterovirus 71 [Formula: see text] targeting Inhibitors
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Rominah Onintsoa, Diarimalala, Meichun, Hu, Yanhong, Wei, and Kanghong, Hu
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Enterovirus 71 life cycle ,Drug Evaluation, Preclinical ,\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$3{\rm C}^{{\rm pro}}$$\end{document}3Cpro functions ,Review ,Antiviral Agents ,\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$3{\rm C}^{{\rm pro}}$$\end{document}3Cpro inhibitors ,Enterovirus A, Human ,Mice ,Animals ,Humans ,RNA, Viral ,Enterovirus 71 ,Enzyme Inhibitors ,Child ,Hand, Foot and Mouth Disease ,Phylogeny ,Nucleic Acid Synthesis Inhibitors ,EV71 drugs screening - Abstract
With CA16, enterovirus-71 is the causative agent of hand foot and mouth disease (HFMD) which occurs mostly in children under 5 years-old and responsible of several outbreaks since a decade. Most of the time, HFMD is a mild disease but can progress to severe complications such as meningitis, brain stem encephalitis, acute flaccid paralysis (AFP) and even death; EV71 has been identified in all severe cases. Therefore, it is actually one of the most public health issues that threatens children’s life. \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$3{\rm C}^{{\rm pro}}$$\end{document}3Cpro is a protease which plays important functions in EV71 infection. To date, a lot of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$3{\rm C}^{{\rm pro}}$$\end{document}3Cpro inhibitors have been tested but none of them has been approved yet. Therefore, a drug screening is still an utmost importance in order to treat and/or prevent EV71 infections. This work highlights the EV71 life cycle, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$3{\rm C}^{{\rm pro}}$$\end{document}3Cpro functions and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$3{\rm C}^{{\rm pro}}$$\end{document}3Cpro inhibitors recently screened. It permits to well understand all mechanisms about \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$3{\rm C}^{{\rm pro}}$$\end{document}3Cpro and consequently allow further development of drugs targeting \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$3{\rm C}^{{\rm pro}}$$\end{document}3Cpro. Thus, this review is helpful for screening of more new \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$3{\rm C}^{{\rm pro}}$$\end{document}3Cpro inhibitors or for designing analogues of well known \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$3{\rm C}^{{\rm pro}}$$\end{document}3Cpro inhibitors in order to improve its antiviral activity.
- Published
- 2020
8. PELP1 Suppression Inhibits Gastric Cancer Through Downregulation of c-Src-PI3K-ERK Pathway
- Author
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Liu Shangqin, Wuhan Xiao, Hongzhu Yan, Ma Zi, Yuanpeng Sun, Zhe Wu, Wu Qian, Ning Zhifeng, Yanling Sun, Yusi Liu, Meichun Hu, and Liu Fuxing
- Subjects
0301 basic medicine ,Cancer Research ,Cell ,Biology ,medicine.disease_cause ,lcsh:RC254-282 ,03 medical and health sciences ,0302 clinical medicine ,Western blot ,oncogene ,medicine ,PELP1 ,chlorpromazine ,PI3K/AKT/mTOR pathway ,Original Research ,Oncogene ,medicine.diagnostic_test ,gastric cancer ,therapeutic target ,Cancer ,master gene ,Cell cycle ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,Cell culture ,030220 oncology & carcinogenesis ,Cancer research ,c-Src-PI3K-ERK pathway ,Carcinogenesis - Abstract
Background: Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1), a co-activator of estrogen receptors alpha, was confirmed to be directly associated with the oncogenic process of multiple cancers, especially hormone-dependent cancers. The purpose of our research was to explore the biological function, clinical significance, and therapeutic targeted value of PELP1 in gastric cancer (GC). Methods: The expression status of PELP1 in GC cell lines or tissues was analyzed through bioinformatics data mining. Thirty-six GC tissue chip was applied to demonstrate the results of bioinformatics data mining assayed by immunohistochemical method. The expression status of PELP1 in GC cell lines was also analyzed using western blot. Correlation analysis between PELP1 expression and clinicopathological parameter was performed. Kaplan-Meier survival analysis was applied to analyze the relationship between PELP1 expression and total survival time. Three pairs of siRNA were designed to silence the expression of PELP1 in GC. After PELP1 was silenced by siRNA or activated by saRNA, the growth, plate colony formation, migration and invasion ability of the GC cell or normal gastric epithelium cell line was tested in vitro. Cell cycle was tested by flow cytometry. Nude mice xenograft experiment was performed after PELP1 was silenced. The downstream molecular pathway regulated by PELP1 was explored. Molecular docking tool was applied to combine chlorpromazine with PELP1. The inhibitory effect of chlorpromazine in GC was assayed, then it was tested whether PELP1 was a therapeutic target of chlorpromazine in GC. Results: PELP1 expression was elevated in GC cell lines and clinical GC tissue samples. PELP1 silence by siRNA compromised the malignant traits of GC. PELP1 expression positively correlated with tumor invasion depth, lymph node metastasis, tissue grade, TNM stage, but had no correlation with patient age, sex, tumor size, and tumor numbers. Kaplan-Meier survival analysis revealed high PELP1 expression had a shorter survival period in GC patients after follow-up. Q-PCR and western blot revealed PELP1 suppression in GC decreased expression of the c-Src-PI3K-ERK pathway. It was also implied that chlorpromazine (CPZ) can inhibit the malignant traits of GC and downregulate the expression of PELP1. Conclusions: In a word, PELP1 is an oncogene in gastric cancer and c-Src-PI3K-ERK pathway activation may be responsible for its tumorigenesis, PELP1 may be a potential therapeutic target of chlorpromazine in GC.
- Published
- 2020
9. Targeting Pyruvate Carboxylase by a Small Molecule Suppresses Breast Cancer Progression
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Meichun Hu, Qingxiang Lin, Zhengfang Yi, Z. Sun, Xue Wang, Tao Zhang, Mingyao Liu, Yihua Chen, Yundong He, Yong Zhang, Yuan He, Weikai Guo, and Li Lai
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General Chemical Engineering ,cancer metabolism ,General Physics and Astronomy ,Medicine (miscellaneous) ,02 engineering and technology ,pyruvate carboxylase ,010402 general chemistry ,01 natural sciences ,Biochemistry, Genetics and Molecular Biology (miscellaneous) ,Metastasis ,breast cancer ,medicine ,General Materials Science ,lcsh:Science ,Wnt/β‐catenin/Snail pathway ,Full Paper ,Chemistry ,General Engineering ,Wnt signaling pathway ,Cancer ,Full Papers ,021001 nanoscience & nanotechnology ,medicine.disease ,0104 chemical sciences ,Pyruvate carboxylase ,Citric acid cycle ,Catenin ,Cancer cell ,Cancer research ,lcsh:Q ,Signal transduction ,0210 nano-technology ,small molecule ZY‐444 - Abstract
Rapid metabolism differentiates cancer cells from normal cells and relies on anaplerotic pathways. However, the mechanisms of anaplerosis‐associated enzymes are rarely understood. The lack of potent and selective antimetabolism drugs restrains further clinical investigations. A small molecule ZY‐444 ((N 4‐((5‐(4‐(benzyloxy)phenyl)‐2‐thiophenyl)methyl)‐N 2‐isobutyl‐2,4‐pyrimidinediamine) is discovered to inhibit cancer cell proliferation specifically, having potent efficacies against tumor growth, metastasis, and recurrence. ZY‐444 binds to cellular pyruvate carboxylase (PC), a key anaplerotic enzyme of the tricarboxylic acid cycle, and inactivates its catalytic activity. PC inhibition suppresses breast cancer growth and metastasis through inhibiting the Wnt/β‐catenin/Snail signaling pathway. Lower PC expression in patient tumors is correlated with significant survival benefits. Comparative profiles of PC expression in cancer versus normal tissues implicate the tumor selectivity of ZY‐444. Overall, ZY‐444 holds promise therapeutically as an anti‐cancer metabolism agent., A specific metabolic inhibitor (named ZY‐444) of pyruvate carboxylase (PC), the key anaplerosis enzyme, is discovered to exhibit cancer selectivity as well as great therapeutic efficacy against breast cancer progression. This study also demonstrates the mechanistic roles of PC in breast cancer progression and identifies the crosstalk between the canonical Wnt pathway and cancer anaplerosis.
- Published
- 2020
10. Lycorine inhibits glioblastoma multiforme growth through EGFR suppression
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Ni Zhu, Zexia Wang, Jia Shen, Meichun Hu, Li Lin, Haotian Yi, Zheng Cheng, Hua Wang, and Tao Zhang
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EGFRvIII ,0301 basic medicine ,Cancer Research ,MMP9 ,Glioblastoma multiforme ,Lycorine ,lcsh:RC254-282 ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,EGFR signaling pathway ,In vivo ,Cell Line, Tumor ,Animals ,Humans ,Epidermal growth factor receptor ,Kinase activity ,Protein kinase B ,Tumor growth ,Gene knockdown ,biology ,Cell growth ,Chemistry ,Research ,Wild type EGFR ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Xenograft Model Antitumor Assays ,Phenanthridines ,ErbB Receptors ,030104 developmental biology ,Oncology ,Amaryllidaceae Alkaloids ,Cancer research ,biology.protein ,Glioblastoma ,Signal Transduction - Abstract
Background Lycorine has been revealed to inhibit the development of many kinds of malignant tumors, including glioblastoma multiforme (GBM). Although compelling evidences demonstrated Lycorine’s inhibition on cancers through some peripheral mechanism, in-depth mechanism studies of Lycotine’s anti-GBM effects still call for further exploration. Epidermal Growth Factor Receptor (EGFR) gene amplification and mutations are the most common oncogenic events in GBM. Targeting EGFR by small molecular inhibitors is a rational strategy for GBM treatment. Methods The molecular docking modeling and in vitro EGFR kinase activity system were employed to identify the potential inhibitory effects of Lycorine on EGFR. And the Biacore assay was used to confirm the direct binding status between Lycorine and the intracellular EGFR (696–1022) domain. In vitro assays were conducted to test the suppression of Lycorine on the biological behavior of GBM cells. By RNA interference, EGFR expression was reduced then cells underwent proliferation assay to investigate whether Lycorine’s inhibition on GBM cells was EGFR-dependent or not. RT-PCR and western blotting analysis were carried out to investigate the underlined molecular mechanism that Lycorine exerted on EGFR itself and EGFR signaling pathway. Three different xenograft models (an U251-luc intracranially orthotopic transplantation model, an EGFR stably knockdown U251 subcutaneous xenograft model and a patient-derived xenograft model) were performed to verify Lycorine’s therapeutic potential on GBM in vivo. Results We identified a novel small natural molecule Lycorine binding to the intracellular EGFR (696–1022) domain as an inhibitor of EGFR. Lycorine decreased GBM cell proliferation, migration and colony formation by inducing cell apoptosis in an EGFR-mediated manner. Furthermore, Lycorine inhibited the xenograft tumor growths in three animal models in vivo. Besides, Lycorine impaired the phosphorylation of EGFR, AKT, which were mechanistically associated with expression alteration of a series of cell survival and death regulators and metastasis-related MMP9 protein. Conclusions Our findings identify Lycorine directly interacts with EGFR and inhibits EGFR activation. The most significant result is that Lycorine displays satisfactory therapeutic effect in our patient-derived GBM tumor xenograft, thus supporting the conclusion that Lycorine may be considered as a promising candidate in clinical therapy for GBM.
- Published
- 2018
11. Inhibition of non-small cell lung cancer (NSCLC) growth by a novel small molecular inhibitor of EGFR
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Xinghai Yang, Jinsong Li, Huayun Deng, Song Wu, Yuanzhang Fang, Leqin Xu, Shijie Chen, Zhenxi Li, Xiaopan Cai, Amanda Vaughn, Jianru Xiao, Meichun Hu, and Wei Wan
- Subjects
Lung Neoplasms ,Time Factors ,Protein Conformation ,non-small cell lung cancer (NSCLC) ,Apoptosis ,NSCLC ,Carcinoma, Non-Small-Cell Lung ,Molecular Targeted Therapy ,Epidermal growth factor receptor ,Phosphorylation ,Mitogen-Activated Protein Kinase 1 ,Mitogen-Activated Protein Kinase 3 ,Gefitinib ,Tumor Burden ,ErbB Receptors ,G2 Phase Cell Cycle Checkpoints ,Molecular Docking Simulation ,Oncology ,Signal transduction ,Signal Transduction ,Research Paper ,medicine.drug ,EGFR ,Mice, Nude ,Antineoplastic Agents ,Biology ,Transfection ,In vivo ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Kinase activity ,Protein Kinase Inhibitors ,Protein kinase B ,Tumor growth ,Cell Proliferation ,Dose-Response Relationship, Drug ,Cell growth ,medicine.disease ,Xenograft Model Antitumor Assays ,respiratory tract diseases ,TKIs ,Mutation ,Quinazolines ,Cancer research ,biology.protein ,Proto-Oncogene Proteins c-akt ,Carbolines - Abstract
The epidermal growth factor receptor (EGFR) is a therapeutic target (oncotarget) in NSCLC. Using in vitro EGFR kinase activity system, we identified a novel small molecule, WB-308, as an inhibitor of EGFR. WB-308 decreased NSCLC cell proliferation and colony formation, by causing G2/M arrest and apoptosis. Furthermore, WB-308 inhibited the engraft tumor growths in two animal models in vivo (lung orthotopic transplantation model and patient-derived engraft mouse model). WB-308 impaired the phosphorylation of EGFR, AKT, and ERK1/2 protein. WB-308 was less cytotoxic than Gefitinib. Our study suggests that WB-308 is a novel EGFR-TKI and may be considered to substitute for Gefitinib in clinical therapy for NSCLC.
- Published
- 2015
12. Suppression of Non-Small Cell Lung Cancer Growth and Metastasis by a Novel Small Molecular Activator of RECK
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Banghua Wang, Zexia Wang, Tao Zhang, Jia Shen, Meichun Hu, Ni Zhu, Jing Jin, and Yi He
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0301 basic medicine ,Lung Neoplasms ,Tumor suppressor gene ,Physiology ,Cell ,Transplantation, Heterologous ,Mice, Nude ,Apoptosis ,NSCLC ,GPI-Linked Proteins ,lcsh:Physiology ,Metastasis ,Cell Line ,lcsh:Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Harmine ,Gentamicin protection assay ,Cell Movement ,Carcinoma, Non-Small-Cell Lung ,medicine ,Animals ,Humans ,lcsh:QD415-436 ,Viability assay ,RECK ,Cell Proliferation ,lcsh:QP1-981 ,Cell growth ,Cell migration ,Cadherins ,Antineoplastic Agents, Phytogenic ,G1 Phase Cell Cycle Checkpoints ,respiratory tract diseases ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Matrix Metalloproteinase 9 ,A549 Cells ,030220 oncology & carcinogenesis ,S Phase Cell Cycle Checkpoints ,Cancer research ,Peganum ,Signal Transduction - Abstract
Background/Aims: Reversion-inducing cysteine-rich protein with kazal motifs (RECK) is a novel tumor suppressor gene that is critical for regulating tumor cell invasion and metastasis. The expression of RECK is dramatically down-regulated in human cancers. Harmine, a tricyclic compound from Peganum harmala, has been shown to have potential anti-cancer activity. Methods: Cell proliferation assay (CCK-8 cell viability assay), cell cycle analysis (detection by flow cytometry), apoptosis staining assay (TUNEL staining), cell migration assay and invasion assay (transwell assay) were carried out to investigate the Harmine’s efficacy on non-small cell lung cancer (NSCLC) cells in vitro. A549-luciferase cell orthotropic transplantation xenograft mouse model was used to determine the effect of Harmine treatment on NSCLC in vivo. Western blotting analysis of cell growth and metastasis related signal pathways was conducted to investigate the molecular mechanism of Harmine’s inhibitory effect on NSCLC. Results: Harmine treatment effectively inhibited cell proliferation and induced the G1/S cell cycle arrest of NSCLC cells. Further study proved that Harmine treatment led to apoptosis induction. Furthermore, treatment with NSCLC cells with Hamine resulted in decreased cell migration and cell invasion in vitro. More importantly, Harmine treatment significantly suppressed the NSCLC tumor growth and metastasis in mouse xenograft model in vivo. Mechanistically, in Harmine-treated NSCLC cells, RECK expression and its downstream signaling cascade were dramatically activated. As a consequence, the expression level of MMP-9 and E-cadherin were significantly decreased. Conclusion: These findings identify Harmine as a promising activator of RECK signaling for metastatic NSCLC treatment.
- Published
- 2017
13. Magnolol Inhibits the Growth of Non-Small Cell Lung Cancer via Inhibiting Microtubule Polymerization
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Hui Liu, Huishuang Li, Jia Shen, Hailin Ma, Guosheng Li, Tiancheng Zhang, Linghua Yu, and Meichun Hu
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0301 basic medicine ,Male ,Mitotic index ,Lung Neoplasms ,Physiology ,Transplantation, Heterologous ,Mice, Nude ,Apoptosis ,NSCLC ,Microtubules ,lcsh:Physiology ,Lignans ,Microtubule polymerization ,lcsh:Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Microtubule ,Carcinoma, Non-Small-Cell Lung ,Cell Line, Tumor ,Autophagy ,Animals ,Humans ,lcsh:QD415-436 ,Mitosis ,PI3K/AKT/mTOR pathway ,Cell Proliferation ,lcsh:QP1-981 ,Chemistry ,Cell growth ,TOR Serine-Threonine Kinases ,Biphenyl Compounds ,Cell cycle ,Antineoplastic Agents, Phytogenic ,Magnolol ,Cell biology ,G2 Phase Cell Cycle Checkpoints ,030104 developmental biology ,A549 Cells ,Magnolia ,030220 oncology & carcinogenesis ,M Phase Cell Cycle Checkpoints ,Tumor Suppressor Protein p53 ,Proto-Oncogene Proteins c-akt ,Signal Transduction - Abstract
Background: The tubulin/microtubule system, which is an integral component of the cytoskeleton, plays an essential role in mitosis. Targeting mitotic progression by disturbing microtubule dynamics is a rational strategy for cancer treatment. Methods: Microtubule polymerization assay was performed to examine the effect of Magnolol (a novel natural phenolic compound isolated from Magnolia obovata) on cellular microtubule polymerization in human non-small cell lung cancer (NSCLC) cells. Cell cycle analysis, mitotic index assay, cell proliferation assay, colony formation assay, western blotting analysis of cell cycle regulators, Annexin V-FITC/PI staining, and live/dead viability staining were carried out to investigate the Magnolol’s inhibitory effect on proliferation and viability of NSCLS cells in vitro. Xenograft model of human A549 NSCLC tumor was used to determine the Magnolol’s efficacy in vivo. Results: Magnolol treatment effectively inhibited cell proliferation and colony formation of NSCLC cells. Further study proved that Magnolol induced the mitotic phase arrest and inhibited G2/M progression in a dose-dependent manner, which were mechanistically associated with expression alteration of a series of cell cycle regulators. Furthermore, Magnolol treatment disrupted the cellular microtubule organization via inhibiting the polymerization of microtubule. We also found treatment with NSCLC cells with Magnolol resulted in apoptosis activation through a p53-independent pathway, and autophgy induction via down-regulation of the Akt/mTOR pathway. Finally, Magnolol treatment significantly suppressed the NSCLC tumor growth in mouse xenograft model in vivo. Conclusion: These findings identify Magnolol as a promising candidate with anti-microtubule polymerization activity for NSCLC treatment.
- Published
- 2017
14. Antitumor Action of a Novel Histone Deacetylase Inhibitor, YF479, in Breast Cancer
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Haigang Wu, Mingyao Liu, Yongxiang Zhao, Jingjie Li, Feifei Yang, Meichun Hu, Zhengfang Yi, Yi Peng, Xiaoling Lu, Yihua Chen, Fujun Dai, and Tao Zhang
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Cancer Research ,biology ,medicine.drug_class ,Histone deacetylase inhibitor ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,medicine.disease_cause ,lcsh:RC254-282 ,Metastasis ,Histone ,Breast cancer ,In vivo ,Immunology ,biology.protein ,Cancer research ,medicine ,Viability assay ,Histone deacetylase ,Carcinogenesis - Abstract
Accumulating evidence demonstrates important roles for histone deacetylase in tumorigenesis (HDACs), highlighting them as attractive targets for antitumor drug development. Histone deactylase inhibitors (HDACIs), which have shown favorable anti-tumor activity with low toxicity in clinical investigations, are a promising class of anticancer therapeutics. Here, we screened our compound library to explore small molecules that possess anti-HDAC activity and identified a novel HDACI, YF479. Suberoylanilide hydroxamic acid (SAHA), which was the first approved HDAC inhibitor for clinical treatment by the FDA, was as positive control in our experiments. We further demonstrated YF479 abated cell viability, suppressed colony formation and tumor cell motility in vitro. To investigate YF479 with superior pharmacodynamic properties, we developed spontaneous and experimental breast cancer animal models. Our results showed YF479 significantly inhibited breast tumor growth and metastasis in vivo. Further study indicated YF479 suppressed both early and end stages of metastatic progression. Subsequent adjuvant chemotherapy animal experiment revealed the elimination of local-regional recurrence (LRR) and distant metastasis by YF479. More important, YF479 remarkably prolonged the survival of tumor-bearing mice. Intriguingly, YF479 displayed more potent anti-tumor activity in vitro and in vivo compared with SAHA. Together, our results suggest that YF479, a novel HDACI, inhibits breast tumor growth, metastasis and recurrence. In light of these results, YF479 may be an effective therapeutic option in clinical trials for patients burdened by breast cancer.
- Published
- 2014
15. Isomangiferin, a Novel Potent Vascular Endothelial Growth Factor Receptor 2 Kinase Inhibitor, Suppresses Breast Cancer Growth, Metastasis and Angiogenesis
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Zexia Wang, Jia Shen, Jianxia Liu, Zhifeng Ning, Banghua Wang, and Meichun Hu
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0301 basic medicine ,Cancer Research ,Angiogenesis ,Angiogenesis inhibitors ,Apoptosis ,Metastasis ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,Isomangiferin ,Kinase ,business.industry ,Cancer ,Kinase insert domain receptor ,medicine.disease ,Vascular endothelial growth factor receptor-2 ,Vascular endothelial growth factor ,030104 developmental biology ,Oncology ,chemistry ,030220 oncology & carcinogenesis ,Cancer research ,Original Article ,Breast neoplasms ,Signal transduction ,business - Abstract
Purpose Vascular endothelial growth factor (VEGF) signal transduction mainly depends on its binding to VEGF receptor 2 (VEGFR-2). VEGF downstream signaling proteins mediate several of its effects in cancer progression, including those on tumor growth, metastasis, and blood vessel formation. The activation of VEGFR-2 signaling is a hallmark of and is considered a therapeutic target for breast cancer. Here, we report a study of the regulation of the VEGFR-2 signaling pathway by a small molecule, isomangiferin. Methods A human breast cancer xenograft mouse model was used to investigate the efficacy of isomangiferin in vivo. The inhibitory effect of isomangiferin on breast cancer cells and the underlying mechanism were examined in vitro. Results Isomangiferin suppressed tumor growth in xenografts. In vitro, isomangiferin treatment inhibited cancer cell proliferation, migration, invasion, and adhesion. The effect of isomangiferin on breast cancer growth was well coordinated with its suppression of angiogenesis. A rat aortic ring assay revealed that isomangiferin significantly inhibited blood vessel formation during VEGF-induced microvessel sprouting. Furthermore, isomangiferin treatment inhibited VEGF-induced proliferation of human umbilical vein endothelial cells and the formation of capillary-like structures. Mechanistically, isomangiferin induced caspase-dependent apoptosis of breast cancer cells. Furthermore, VEGF-induced activation of the VEGFR-2 kinase pathway was down-regulated by isomangiferin. Conclusion Our findings demonstrate that isomangiferin exerts anti-breast cancer effects via the functional inhibition of VEGFR-2. Pharmaceutically targeting VEGFR-2 by isomangiferin could be an effective therapeutic strategy for breast cancer.
- Published
- 2018
16. LG308, a Novel Synthetic Compound with Antimicrotubule Activity in Prostate Cancer Cells, Exerts Effective Antitumor Activity
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Shihong Peng, Yihua Chen, Ning Liu, Zhengfang Yi, Mingyao Liu, Yuan He, Meichun Hu, Huang Chen, Min Qin, Guoliang Li, Ang Chen, Xin Wang, and Yundong He
- Subjects
G2 Phase ,Male ,Mitotic index ,Mice, Nude ,Mitosis ,Antineoplastic Agents ,Apoptosis ,Biology ,Microtubules ,chemistry.chemical_compound ,Prostate cancer ,Mice ,Microtubule ,Cell Line, Tumor ,LNCaP ,CDC2 Protein Kinase ,medicine ,Mitotic Index ,Animals ,Humans ,Cyclin B1 ,Tumor Stem Cell Assay ,Cell Proliferation ,Pharmacology ,Dose-Response Relationship, Drug ,Cell growth ,Forkhead Box Protein M1 ,Prostatic Neoplasms ,Forkhead Transcription Factors ,medicine.disease ,Xenograft Model Antitumor Assays ,Tubulin Modulators ,Cell biology ,Tubulin ,Paclitaxel ,chemistry ,biology.protein ,Molecular Medicine ,Cell Division - Abstract
Microtubule plays many different essential roles in the process of tumorigenesis in many eukaryotes, and targeting mitotic progression by disturbing microtubule dynamics is used as a common strategy for cancer treatment. Microtubule-targeted drugs, including paclitaxel and Vinca alkaloids, were previously considered to work primarily by increasing or decreasing the cellular microtubule mass. The tubulin/microtubule system, which is an integral component of the cytoskeleton, is a therapeutic target for prostate cancer. In this study, we found a novel synthetic compound, 8-fluoro-N-phenylacetyl-1, 3, 4, 9-tetrahydro-β-carboline (LG308), which disrupted the microtubule organization via inhibiting the polymerization of microtubule in PC-3M and LNCaP prostate cancer cell lines. Further study proved that LG308 induced mitotic phase arrest and inhibited G2/M progression significantly in LNCaP and PC-3M cell lines in a dose-dependent manner, and these were associated with the upregulation of cyclin B1 and mitotic marker MPM-2 and the dephosphorylation of cdc2. Besides, the cell proliferation and colony formation of PC-3M and LNCaP cells were effectively inhibited by LG308. Furthermore, LG308 induced apoptosis and cell death in PC-3M and LNCaP cell lines in vitro. In vivo, LG308 dramatically suppressed the growth and metastasis of prostate cancer in both xenograft and orthotopic models. All these data indicate that LG308 is a promising anticancer candidate with antimitotic activity for the treatment of prostate cancer.
- Published
- 2015
17. Lycorine is a novel inhibitor of the growth and metastasis of hormone-refractory prostate cancer
- Author
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Min Qin, Shihong Peng, Xiaonan Cong, Xing Yajing, Meichun Hu, Mingyao Liu, Zhengfang Yi, and Yundong He
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Male ,STAT3 Transcription Factor ,Epithelial-Mesenchymal Transition ,Cell Survival ,Transplantation, Heterologous ,Mice, Nude ,Context (language use) ,Antineoplastic Agents ,Apoptosis ,Pharmacology ,Lycorine ,Metastasis ,Prostate cancer ,chemistry.chemical_compound ,Mice ,hormone-refractory PCa ,Cell Movement ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Neoplasm Invasiveness ,Epithelial–mesenchymal transition ,Neoplasm Metastasis ,Amaryllidaceae Alkaloids ,tumor growth and metastasis ,Cell Proliferation ,Epidermal Growth Factor ,Cell growth ,business.industry ,Cancer ,Prostatic Neoplasms ,medicine.disease ,Phenanthridines ,Gene Expression Regulation, Neoplastic ,STAT3 signaling ,Oncology ,chemistry ,Drug Resistance, Neoplasm ,business ,Neoplasm Transplantation ,Signal Transduction ,Research Paper - Abstract
// Meichun Hu 1 , Shihong Peng 1 , Yundong He 1 , Min Qin 1 , Xiaonan Cong 1 , Yajing Xing 1 , Mingyao Liu 1, 2 , Zhengfang Yi 1 1 Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China 2 Institute of Bioscience and Technology, Texas A&M University Health Science Center, Houston, Texas 77030, USA Correspondence to: Zhengfang Yi, e-mail: zfyi@bio.ecnu.edu.cn Keywords: Lycorine, hormone-refractory PCa, STAT3 signaling, tumor growth and metastasis Received: January 06, 2015 Accepted: March 15, 2015 Published: April 12, 2015 ABSTRACT Lycorine, a natural alkaloid extracted from the Amaryllidaceae plant family, has been reported to exhibit a wide range of physiological effects, including the potential effect against cancer. However, the anti-prostate cancer (PCa) efficacy of Lycorine remains unrevealed. In this context, we figured out Lycorine’s anti-proliferative and anti-migratory properties for PCa treatment. Lycorine inhibited proliferation of various PCa cell lines, induced cell apoptosis and cell death. Here we showed that Lycorine decreased proliferation, migration, invasion, survival and EMT of prostate cancer cell lines. Subcutaneous and orthotopic xenotransplantations by ectopic implantation of the human hormone-refractory PC-3M-luc cells were used to confirm in vivo anticancer effects of Lycorine. Lycorine inhibited both growth and metastasis in multiple organs (liver, lung, kidney, spleen and bone) in vivo and improved mice survival. Lycorine prevented EGF-induced JAK/STAT signaling. Importantly, anti-cancer effects of Lycorine were dependent on STAT expression. We suggest that Lycorine is a potential therapeutic in prostate cancer.
- Published
- 2015
18. A new nasal cavity nursing methods application in patients with mechanical ventilation
- Author
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Liuqing Wei, Meichun Hu, Fufu Jiang, Gang Qin, Xining Yang, and Tianwei Lai
- Subjects
Mechanical ventilation ,Nasal cavity ,medicine.medical_specialty ,APACHE II ,business.industry ,medicine.medical_treatment ,Ventilator-associated pneumonia ,General Medicine ,medicine.disease ,Atomizing nasal cleaning method ,Group A ,Group B ,Surgery ,Pneumonia ,medicine.anatomical_structure ,Nursing ,Anesthesia ,Ventilator- associated pneumonia ,medicine ,Original Article ,business ,Saline - Abstract
Objective To compare different nasal cavity nursing methods on mechanically ventilated patients. Methods According to acute physiology and chronic health evaluation (APACHEII), 615 cases of mechanically ventilated patients were divided into group A, group B and group C by stratified random method. Traditional oral nursing plus aspirating secretions from oral cavity and nasal cavity q6h were done in group A. Based on methods in group A, normal saline was used for cleaning nasal cavity in group B. Besides the methods in group A, atomizing nasal cleansing a6h was also used in group C. Incidence rate of Ventilator-Associated Pneumonia (VAP) and APACHE II scores after administrating were compared. The correlation between APACHE II score and outcomes was analyzed by Spearman-rank correlation. Results In group A, incidence of VAP was 36.76%, group B was 30.24%, group C was 20.38%, and the difference was statistically significant. APACHE II scores in group C were significantly lower compared with group A and B. APACHE II score was negatively correlated with clinical outcomes. Conclusions For mechanically ventilated patients, nasal nursing can't be ignored and the new atomizing nasal cleaning is an effective method for VAP prevention.
- Published
- 2013
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