Background: Cisplatin is a commonly used drug for the treatment of various types of malignant cancers, including ovarian cancer. However, resistance to cisplatin is still a considerable obstacle to achieve a satisfactory therapeutic effect. The purpose of this study is to develop a strategy to sensitize ovarian cancer cells to cisplatin-induced cytotoxicity.
Methods: miR-34c levels in ovarian cancer tissues and cell lines were tested by qRT-PCR analysis. In vitro assays, the effect of miR-34c on cisplatin was evaluated by using MTT. Expression of MET and phosphorylation of PI3K and AKT were tested by Western blot assays. Conjugation with Bad and Bcl-xl was evaluated through immunoprecipitation. Flow cytometry analysis was performed to measure the apoptotic rate of ovarian cancer cells.
Results: Downregulation of miR-34c was observed in ovarian cancer tissues and cell lines. However, miR-34c overexpression was found to sensitize ovarian cancer cells to cisplatin treatment in vitro and in vivo. Mechanically, we found that miR-34c targeted the MET gene, thereby inhibiting the phosphorylation of PI3K and AKT to activate Bad. As a result, miR-34c reduced resistance of ovarian cancer cells to cisplatin-induced apoptosis.
Conclusion: miR-34c/MET axis promotes cisplatin-induced cytotoxicity against ovarian cancer by targeting the MET/PI3K/AKT/Bad pathway.
Keywords: ovarian cancer, miR-34c, cisplatin, MET, Bad