Regulatory Effects and Associated Mechanisms of miR-130a Molecules on Cisplatin Resistance in Ovarian Cancer A2780 Cell Lines

Abstract

To determine the regulatory effects and associated mechanisms of miR-130a on cisplatin resistance in ovarian cancer A2780 cell lines （including cisplatin sensitive A2780s and its resistant A2780/DDP cells）. Methods A2780s and A2780/DDP cells were divided into four groups, and treated with lipo2000 (Lip), miR-negative （miR-NC） control, miR-130a-mimics (miR-130a-M increasing the expression of miR-130a and the agent), and miR-130a-inhibitor (miR-130a-I downregulating miR-130a expression), respectively. The proliferation of cells and their sensitivity to cisplatin were detected by MTT assay. RT-PCR and western blot were performed to examine the levels of MDR1, PTEN mRNA and proteins. Results The expressions of MDR1 mRNA and P-gp in the A2780/DDP cells were significantly higher than those in the A2780s cells. However, no differences in the expressions of PTEN mRNA and proteins were detected between the two cell lines. Over-expressions of miR-130a had no effect on cell proliferation, but increased the resistance of the cells to cisplatin and up-regulated the expressions of MDR1 mRNA and P-gp in both cell lines. Down-regulated miR-130a did not affect cell proliferations, but enhanced the sensitivity of the cells to cisplatin, inhibited the expressions of MDR1 mRNA and P-gp and increased the expression of PTEN proteins. Conclusion MiR-130a expression may be associated with cisplatin resistance of ovarian cancer cells. MiR-130a inhibitor can reverse the cisplatin resistance by up-regulating the expression of PTEN proteins and down-regulating P-gp in A2780 cell lines. MiR-130 may become a new potential target of genetic therapy for cisplatin-resistant ovarian cancers.

Key words: Ovarian cancer Cisplatin resistance miR-130a PTEN MDR1 P-gp