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Omega-3 has been proposed as an antitumor substance that suppresses the growth and metastasis of multiple types of tumor cells, including lung cancer, but the specific mechanisms involved remain obscure. Our previous studies showed that the expression of chemokine ligand 18 was related to the migration and metastasis of non-small cell lung cancer. Here, we aim to explore whether omega-3 inhibits invasion and metastasis of NSCLC by regulating the expression of CCL18. The expression of CCL18, metastasis- and epithelial-mesenchymal transition (EMT)-related genes at mRNA and protein levels in NSCLC cell lines were detected by RT-qPCR and Western blot, respectively. The metastatic and invasive capability of NSCLC cells were evaluated by scratch wound healing and Transwell assays, respectively. Our results showed that the level of CCL18 is positively associated with metastatic ability of NSCLC cells. Docosahexaenoic acid, an important long-chain, polyunsaturated omega-3 (n−3) fatty acid, significantly inhibited invasion and metastasis of NSCLC cells, and concomitantly downregulated the expression of metastasis- and EMT-related genes and p-STAT3 signaling pathway. Additionally, we found that DHA inhibited CCL18 expression in lung cancer cells, while overexpression of CCL18 effectively reversed DHA-mediated downregulation in the expression of metastasis- and EMT-related genes and p-STAT3 signaling as well as DHA-mediated inhibitory effect on metastasis and invasion of NSCLC cells. DHA inhibits NSCLC cell invasion and metastasis possibly through targeted inhibition of CCL18/ STAT3 signaling pathway and EMT process.

Aim To explore the effect of miR-296-5p on the metastasis of nasopharyngeal carcinoma (NPC) cells and investigate the underlying mechanism. Methods The expressions of miR-296-5p in NPC tissues and cells were determined using GSE32920 database analysis and real-time PCR and miRNA microarray assays. An miR-296-5p mimic and inhibitor were transfected into NPC cells. Then, immunofluorescence imaging, scratch wound-healing, transwell migration and invasion assays were used to observe the effects of miR-296-5p on cell metastasis and invasion. Real-time PCR and western blotting were carried out to detect the expressions of genes and proteins related to epithelial–mesenchymal transition (EMT). A dual luciferase reporter assay was used to identify whether TGF-β is the target gene of miR-296-5p. Finally, TGF-β expression plasmids were transfected into NPC cells to verify the role of TGF-β in the miR-296-5p-mediated inhibition of nasopharyngeal carcinoma cell metastasis. Results Our results show that miR-296-5p inhibits the migratory and invasive capacities of NPC cells by targeting TGF-β, which suppresses EMT. Importantly, the miR-296-5p level was significantly lower in human NPC tissues than in adjacent normal tissues. It also negatively correlated with TGF-β and was significantly associated with the lymph node metastasis of patients with NPC. Conclusions Our findings show that miR-296-5p represses the EMT-related metastasis of NPC by targeting TGF-β. This provides new insight into the role of miR-296-5p in regulating NPC metastasis and invasiveness.

Difluoroisoxazolacetophenone (DFIO) is developed as a new difluoroalkylation reagent that can be easily prepared from inexpensive starting materials. In situ remote C–C bond cleavage of DFIO afford...

Objective:Nasopharyngeal carcinoma is highly endemic in Southeast China. Circulating tumor cell is an important biomarker in the prognosis of variety kinds of cancers. Overexpression of fibronectin 1 was observed in variety kinds of malignancies and may contribute to progress and metastasis of the cancers. The current study was aimed to investigate phenotypes of circulating tumor cell in nasopharyngeal carcinoma blood and fibronectin 1 expression in the circulating tumor cell, and their clinical application in predicting nasopharyngeal carcinoma prognosis.Methods:Blood samples were obtained from nasopharyngeal carcinoma patients before and after treatment. CanPatrol circulating tumor cell enrichment and RNA in situ hybridization were applied to identify circulating tumor cell and its phenotypes. Fibronectin 1 messenger RNA expression in the cells of circulating tumors was examined by messenger RNA-in situ hybridization.Results:Circulating tumor cell was not associated with tumor characteristics or lymph node metastasis. Patients with >9 circulating tumor cells or >5 mesenchymal phenotype circulating tumor cell per 5-mL blood had poorer progression-free survival ( P < .05). Multivariable analysis demonstrated that 2 or more mesenchymal phenotype circulating tumor cells with high fibronectin 1 messenger RNA expression predicted shorter progression-free survival ( P < .05).Conclusions:Circulating tumor cells with high-level fibronectin 1 expression was associated with poor survival in patients with nasopharyngeal carcinoma and could be an independent prognostic factor for nasopharyngeal carcinoma.

The aim of the present study was to investigate whether niclosamide could sensitize the nasopharyngeal carcinoma cells to radiation and further explore the underlying mechanisms. CCK-8 assay was used to determine the effect of niclosamide on the proliferation of NPC cells. Colony formation assay was used to evaluate the radiosensitizing effect of niclosamide on NPC cells. Flow cytometry analysis was used to determine the apoptosis of NPC cells induced by niclosamide. Immunofluorescent staining was used to detect the formation of γ-H2AX foci and the localization of Ku70/80 proteins in NPC cells. Real-time PCR quantification analysis was used to examine the level of Ku70/80 mRNA. DNA damage repair-related proteins were detected by western blot analysis. Our results showed that niclosamide markedly suppressed the proliferation of NPC cells. Niclosamide pretreatment followed by irradiation reduced the colony forming ability of NPC cells. Niclosamide in combination with irradiation significantly increased the apoptotic rate of NPC cells. Niclosamide significantly reduced the transcriptional level of K70/80 but not the translocation of Ku70/80 protein induced by irradiation. In conclusion, our study demonstrated that niclosamide could inhibit the growth of NPC cells and sensitize the NPC cells to radiation via suppressing the transcription of Ku70/80.

Cancer cells are characterized by a pathological manifestation of uncontrolled proliferation, which results in tumor formation. Therefore, it is necessary to improve understanding of the underlying mechanism of cell cycle control. Here, we report that miR‑150 is downregulated in nasopharyngeal carcinoma tissues and cells. Upregulation of miR‑150 suppresses nasopharyngeal carcinoma (NPC) cell proliferation and induces G1/S arrest in vitro, and inhibits tumorigenesis in vivo. Conversely, silencing miR‑150 yields the opposite effect. Our results further demonstrate that miR‑150 retards nasopharyngeal carcinoma cell proliferation and G1/S transition via targeting multiple cell cycle-related genes, including CCND1, CCND2, CDK2 and CCNE2. Therefore, our results uncover a novel mechanistic understanding of miR‑150-mediated tumor suppression in NPC, which will facilitate the development of effective cancer therapies against nasopharyngeal carcinoma.

A direct vinylogous cross-dehydrogenative coupling (CDC) reaction of N-aryl tetrahydroisoquinolines with 3,5-dialkyl-4-nitroisoxazoles catalysed by CuBr using air as the oxidant in water has been developed. This new strategy provides an efficient and environmentally benign way to access medicinally important isoxazole substituted tetrahydroisoquinoline derivatives under mild conditions.

Background: CC chemokine ligand 18 (CCL18) is a chemotactic cytokine involved in the pathogenesis and progression of various cancers. Our previous research showed that the expression of CCL18 is obviously higher in non-small cell lung cancer (NSCLC) than in the adjacent normal tissues, suggesting its role in NSCLC. Methods: We further examined the serum level of CCL18 in 80 NSCLC patients with enzyme-linked immunosorbent assay and simultaneously analyzed the survival curve of these patients by the Kaplan–Meier method, and then utilized a log-rank test to evaluate the correlation of CCL18 expression with the malignant progression of NSCLC. Results: Our results showed that the median serum concentration of CCL18 was significantly elevated to 436.11 ng/mL in NSCLC patients compared to 41.97 ng/ml in healthy people ( PConclusion: Our findings suggest that the serum CCL18 level of NSCLC patients was negatively correlated with the prognosis, thus suggesting that CCL18 may serve as a potential circulating biomarker for NSCLC diagnosis.

An "on water" organocatalytic cyanoarylmethylation of aryl acetonitrile to isatins is developed, giving products in high yields and up to excellent diastereoselectivities. A remarkable enhancement of reaction rates and diastereoselectivities by water was observed under mild conditions. Moreover, this approach provides a highly efficient and environmentally benign access to thermodynamic 3-hydroxy-3-cyanomethyl oxindoles.

An efficient ‘on water’-promoted direct catalytic vinylogous addition of 3,5-dimethyl-4-nitroisoxazole to aldehydes and trifluoromethyl ketones was described, giving Henry (nitroaldol) adducts in excellent yields. The trifluoromethyl tertiary alcohol product could be transformed to the corresponding styrene derivative, which was demonstrated as a new type of Michael acceptor in the vinylogous 1,6-Michael addition with nitromethane.

The selective condensation of pyrazolones with isatins using water as the reaction medium is presented. This strategy provides an environmentally benign synthetic route to synthesize various potentially bioactive pyrazolone substituted oxindoles.

Chemokine (C-C Motif) Ligand 18 (CCL18) is a chemotactic cytokine involved in the pathogenesis and progression of various cancers by activating downstream signaling pathways and affecting cellular behaviors. We conducted a meta-analysis to evaluate the CCL18 as a prognostic marker for cancer and determine the relationship between CCL18 and clinicopathological features of cancer.We searched the PubMed, Cochrane, Embase, Web of Science and SinoMed databases for publications to investigate the association between CCL18 expression and survival outcome in cancer. Hazard ratios (HRs) and 95% confidence intervals (CI) of overall survival (OS) were pooled. Odds ratios (ORs) of clinicopathological features were computed. Meta-analysis was performed using STATA 12.0 software.Our meta-analysis identified a total of 17 studies including 2829 cases. Meta-analysis revealed that the expression of CCL18 in various cancer tissues was significantly higher than that in the normal group (OR=16.694, 95% CI=14.117-27.476, p0.01, random effects). The abnormal expression of CCL18 was associated with lymph node metastasis (OR=4.409, 95% CI=2.129-9.128, p0.01, random effects) and TNM stage (breast cancer subgroup: III+IV vs I+II OR=13.187, 95% CI=8.417-20.660, p0.01; gastric cancer subgroup: III+IV vs I+II OR=0.034, 95% CI=0.008-0.137, p0.01) but is was not related to gender (male vs. female: OR=0.88, 95% CI=0.667-1.162, p=0.368) and age (60 vs. ≤60 years: OR=1.118, 95% CI=0.795-1.571, p-0.522). CCL18 overexpression was associated with poor overall prognosis of breast cancer (Hazard Ratio/HR=2.969, 95% CI=1.361- 6.478, p0.01, random effects).CCL18 is highly expressed in cancer tissues and is closely related to tumor metastasis and prognosis, and its role in tumor development is worth of further study.

The first example of an “on water” direct catalytic vinylogous Henry addition of 3,5-dialkyl-4-nitroisoxazoles to isatins is described, giving products in excellent yields and up to excellent diastereoselectivities. A remarkable rate-enhancement by water was observed under mild conditions. This approach provides a highly efficient and environmentally benign access to medicinally important isoxazole substituted 3-hydroxy-2-oxindole derivatives.

The scalable protocol is applicable to the diastereoselective transformation of 3,5-diethyl-4-nitroisoxazole.

Bax inhibitor-1 (Bi-1), an anti-apoptotic protein that belongs to the Bcl-2 family, plays an important role in the mitochondrial apoptosis pathway to suppress Bax-induced apoptosis. In several human cancers, including nasopharyngeal carcinoma, its expression was found to be increased; however, up-regulated expression of this protein has been linked to increased cell proliferations. In this study, we down-regulated the gene expression of Bi-1 in nasopharyngeal carcinoma cells by using a lentivirus transfection system packed with short hairpin RNA targeting Bi-1 and used an in vivo model to assess its efficacy as a target in human gene therapy. The data indicated that human malignant nasopharyngeal carcinoma cells, CNE-1 and SUNE-1, transfected with lentiviral short hairpin RNA targeting Bi-1 grew more slowly and showed a higher degree of apoptosis. Moreover, the tumorigenicity of CNE-1 was significantly suppressed when inoculated mice were intratumorically injected with the same vector. Taken together, these data lead us to conclude that Bi-1 plays a crucial role in CNE-1 tumorigenesis and that Bi-1 may be a novel therapeutic target for nasopharyngeal carcinoma.

The first example of an “on water” direct catalytic vinylogous Henry addition of 3,5-dialkyl-4-nitroisoxazoles to isatins is described, giving products in excellent yields and up to excellent diastereoselectivities. A remarkable rate-enhancement by water was observed under mild conditions. This approach provides a highly efficient and environmentally benign access to medicinally important isoxazole substituted 3-hydroxy-2-oxindole derivatives.

To investigate the effects of epigallocatechin-3-gallate (EGCG) on the expression of HIF-1α and vascular endothelial growth factor (VEGF) and cell growth in MCF-7 breast cancer cells.MCF-7 human breast cancer cells were pretreated with different concentrations of EGCG (25, 50, 100 mg/L) for 48 h. The growth and proliferation of cells were analyzed by trypan blue staining in the pretreated MCF-7 cells. Furthermore, mRNA expression of HIF-1α and VEGF was detected by reverse transcriptase polymerase chain reaction (RT-PCR) analysis in the pretreated MCF-7 cells. Protein expression of HIF-1α was detected by Western blot, and the secreted protein level of VEGF in the supernatant of the culture medium was analyzed by enzyme linked immuno- sorbent assay (ELISA) in the MCF-7 cells pretreated with different concentrations of EGCG.Cell growth decreased dramatically in MCF-7 cells treated with different concentrations of EGCG, compared with untreated (control) cells. Moreover, protein expression of HIF-1α and VEGF declined in a dose-dependent manner in MCF-7 cells pretreated with increasing concentrations of EGCG.EGCG inhibits cell growth and proliferation of MCF-7 breast cancer cells, possibly by inhibiting the protein expression of HIF-1α and VEGF.

The aim of this study was to construct a recombinant lentiviral expression vector targeting human BAX inhibitor- 1(BI-1) gene and observe its expression in NIH3T3 cells.Human BI-1 gene was amplified by polymerase chain reaction (PCR), and then cloned into the vector pLCMV- IG using DNA recombinant technique. After the inserted sequences in the recombinant plasmids were identified by PCR, and double digesting and DNA sequencing analysis, the recombinant lentivirus was packaged and administered into NIH3T3 cells. The BI-1 mRNA and protein expression were examined by real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting.PCR double digesting analysis and DNA sequencing confirmed that the BI-1 DNA sequences were successfully inserted into the lentiviral vectors. After transfection with the recombinant lentivirus, BI-1 expression in NIH3T3 cells was significantly increased at both mRNA and protein levels.The lentiviral vector expressing BI-1 has been successfully constructed, which allowed for the subsequent analysis of the role of BI-1 in cell growth and transduction.