Abstract
Non-small cell lung cancer (NSCLC) is the most common and lethal human malignant tumor worldwide. Platinum-based chemotherapy is still the mainstay treatment for NSCLC. However, long-term chemotherapy usually induces serious drug resistance. Accordingly, it is valuable to develop treatment strategies that could reduce the resistance against platinum-based drugs in NSCLC cells. Cisplatin-resistant NSCLC models in A549 and PC9 cell lines (CR-A549 and CR-PC9) were established through long-term exposure to cisplatin. Expression levels of caveolin-1 (CAV-1) and miR-204 in A549, PC9, CR-A549, and CR-PC9 cell lines were detected by western blot and q-PCR, respectively. Regulation of CAV-1 by miR-204 was assessed by bioinformatic analysis, western blot and luciferase reporter assay. The role of the miR-204/CAV-1 axis in regulating cisplatin resistance in NSCLC cells was tested by MTT assay. Interactions with Bcl-2-associated agonist of cell apoptosis (Bad) and Bcl-xl (Bcl-2) were evaluated by co-immunoprecipitation assay. Flow cytometry was used to detect the apoptosis of NSCLC cell lines. We observed significant upregulation of CAV-1 expression and a significant decrease of miR-204 expression in CR-A549 and CR-PC9 cells compared to their parental A549 and PC9 cells. Furthermore, we detected down regulation of miR cells. We then found that enforced expression of miR-204 can resensitize CR-A549 and CRPC9 cells to cisplatin treatment through the inhibition of CAV-1 expression. Thus, we declared that recovery of miR-204 expression was able to sensitize the cisplatin-induced mitochondrial apoptosis observed in CR-A549 and CR-PC9 cells through suppression of the caveolin-1/AKT/Bad pathway. This study suggested that enhanced expression of miR-204 could increase the sensitivity of cisplatin treatment by suppression of caveolin-1/AKT/Bad pathway, which concluded that overexpression of miR-204 could be a potential approach for enhancing the sensitivity in NSCLC cells with cisplatin resistance.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
