The Role And Molecular Mechanisms Of Docetaxel In Non-small-cell Lung Cancer Through MicroRNA-7 In Vitro

Background:Lung cancer is the leading cause of cancer-related deaths worldwide and about 85% of these are non-small cell lung cancer (NSCLC). Several new chemotherapeutic agents have recently shown encouraging activity in NSCLC, especially docetaxel. MiRNAs (MicroRNAs) are closely related to cancer development. We studied miRNAs in NSCLC cell lines to identify those that can regulate and predict the effectiveness of docetaxel on NSCLC.Methods:CCK8, Annexin and V-FITC assays were carried out to evaluate the inhibitory effect of docetaxel on NSCLC cell lines A549 and H460, and qRT-PCR was used to detect and compare six miRNAs expression levels in the two cells with docetaxel or not. Knockdown of miR-7 by RNA interference and overexpression of miR-7 were taken to evaluate the effect of miR-7 on docetaxel effectiveness. Western blots were used to evaluate the effect of miR-7 on Bcl-2 in A549 and H460 cells.Results:Docetaxel induced non-small cell lung cancer cell apoptosis and suppressed cell proliferation in vitro. MiR-7 expression levels were increased by docetaxel in the two cell lines. MiR-7 over expression improved anti-proliferative and pro-apoptotic effects of docetaxel on the NSCLC cells and that miR-7 down-regulation decreased those effects. Moreover, subsequent experiments showed that BCL-2 was downregulated by miR-7 at both transcriptional and translational levels.Conclusions:This study further extends the biological role of miR-7 in NSCLC A549 and H1299 cells and identifies BCL-2 as a novel target possibly involved in miR-7-mediated growth suppression and apoptosis induction of NSCLC cells.