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Background: Non-small cell lung cancer (NSCLC) is the most common malignancy worldwide. MiR-199a-5p has been reported to play important roles in multiple tumors, inclusive of NSCLC. However, little is definitively known pertaining to its explicit mechanism of action in NSCLC.Methods: The expressions of miR-199a-5p and hypoxia-inducible factor-1α (HIF-1α) mRNA were quantified employing qRT-PCR. H1299 and A549 cells were transiently transfected with miR-199a-5p mimics or inhibitors. Then, CCK-8 assays, flow cytometry analysis, and Transwell assay were performed for detecting cell proliferation, cell cycle, apoptosis, migration, and invasion of NSCLC cells, respectively. HIF-1α, signal transducer and activator of transcription 3 (STAT3), and p-STAT3 expressions were detected via Western blotting. Bioinformatic analysis and dual-luciferase assay were performed to investigate the interactions among miR-199a-5p, HIF-1α, and STAT3. Xenograft models were established with nude mice for further analyzing the bevacizumab resistance of NSCLC cells.Results: MiR-199a-5p expression was markedly attenuated in NSCLC tissues and cell lines. Overexpression of miR-199a-5p repressed the proliferation, migration, and invasion but induced the apoptosis of NSCLC cells. HIF-1α was identified as a direct target of miR-199a-5p. There was a positive feedback loop among miR-199a-5p, HIF-1α, and STAT3. Co-transfection of HIF-1α or STAT3 overexpression plasmids counteracted the effects of miR-199a-5p. In vivo experiments indicated that the feedback loop was in association with the bevacizumab resistance of NSCLC cells.Conclusion: MiR-199a-5p blocked the progression of NSCLC and sensitized NSCLC cells to bevacizumab by suppressing HIF-1α and STAT3, while the HIF-1α/STAT3 axis suppressed the expression of miR-199a-5p, which forms a positive feedback loop to promote the sustaining progression of NSCLC.

That specific immunotherapy can inhibit cancer growth has been recognized; its efficiency is to be improved. This study aimed to inhibit lung cancer (LC) growth in a mouse model by using an LC-specific vaccination. In this study, a LC mouse model was created by adoptive transplantation with LC cells. The tumor-bearing mice were vaccinated with LC cell extracts plus adjuvant TNBS or adoptive transplantation with specific CD8(+) CD196(+) T cells. The results showed that the vaccination with LC extracts (LCE)/TNBS markedly inhibited the LC growth and induced CD8(+) CD196(+) T cells in LC tissue and the spleen. These CD8(+) CD196(+) T cells proliferated and produce high levels of perforin upon exposure to LCE and specifically induced LC cell apoptosis. Exposure to TNBS induced RAW264.7 cells to produce macrophage inflammatory protein-3α; the latter activated signal transducer and activator of transcription 3 and further induced perforin expression in the CD8(+) CD196(+) T cells. Adoptive transfer with specific CD8(+) CD196(+) T cells suppressed LC growth in mice. In conclusion, immunization with LC extracts and TNBS can induce LC-specific CD8(+) CD196(+) T cells in LC-bearing mice and inhibit LC growth.

The apoptotic mechanism dysfunction plays a critical role in cancer cell growth and escaping from cancer therapies; the underlying mechanisms are to be further elucidated. This study aims to investigate the role of phospholipase C epsilon 1 (PLCE1) in modulating the apoptosis mechanism in esophageal cancer (Eca) cells. The results showed that Eca cell lines, OE33 and CP-C cells expressed high levels of PLCE1. Knockdown of PLCE1 markedly increased 9.26 folds of the expression of p53 and 13.8 folds of the frequency of apoptotic CP-C cells via modulating the p53 promoter methylation.

Introduction: The esophagus squamous cell carcinoma (ESCC) is one of the most deadly malignances, and a current challenge is the development of effective therapeutic agents. Our present work addressed the effect of HIF-1α siRNA alone or in combination with cisplatin on the growth of ESCC in nude mice. Materials and Methods: Xenografts were established by inoculating ESCC TE-1 cells in nude mice, and transplanted tumors were treated with HIF-1α siRNA, cisplatin alone or together. Growth was assessed by measuring tumor volume. HIF-1α mRNA and protein expression were detected using RT-PCR and immunohistochemistry, respectively. Apoptosis of ESCC TE-1 cells was analyzed by flow cytometry. Results: In our nude mice model, HIF-1α siRNA effectively inhibited the growth of transplanted ESCC, downregulating HIF-1α mRNA and protein expression, and inducing ESCC TE-1 cell apoptosis. Notably when combinated with cisplatin, HIF-1α siRNA showed synergistic interaction in suppressing tumor growth. Furthermore, the proportion of apoptotic cells in HIF- 1α siRNA plus cisplatin group was significantly higher than that in cisplatin or HIF-1α siRNA-treated groups (P

Background Lung adenocarcinom (AC) is the most common form of lung cancer. Currently, the number of medical options to deal with lung cancer is very limited. In this study, we aimed to investigate potential therapeutic compounds for lung adenocarcinoma based on integrative analysis. Methodology/Principal Findings The candidate therapeutic compounds were identified in a two-step process. First, a meta-analysis of two published microarray data was conducted to obtain a list of 343 differentially expressed genes specific to lung AC. In the next step, expression profiles of these genes were used to query the Connectivity-Map (C-MAP) database to identify a list of compounds whose treatment reverse expression direction in various cancer cells. Several compounds in the categories of HSP90 inhibitor, HDAC inhibitor, PPAR agonist, PI3K inhibitor, passed our screening to be the leading candidates. On top of the list, three HSP90 inhibitors, i.e. 17-AAG (also known as tanespimycin), monorden, and alvespimycin, showed significant negative enrichment scores. Cytotoxicity as well as effects on cell cycle regulation and apoptosis were evaluated experimentally in lung adenocarcinoma cell line (A549 or GLC-82) with or without treatment with 17-AAG. In vitro study demonstrated that 17-AAG alone or in combination with cisplatin (DDP) can significantly inhibit lung adenocarcinoma cell growth by inducing cell cycle arrest and apoptosis. Conclusions/Significance We have used an in silico screening to identify compounds for treating lung cancer. One such compound 17-AAG demonstrated its anti-lung AC activity by inhibiting cell growth and promoting apoptosis and cell cycle arrest.