Inhibition of microRNA-23a increases cisplatin sensitivity of ovarian cancer cells:the possible molecular mechanisms
10.3969/j.issn.1673-4254.2015.01.25
- VernacularTitle:抑制miR-23a表达增强卵巢癌顺铂敏感性的分子机制
- Author:
Aihong JIN
1
;
Xiaping ZHOU
;
Fengzhen ZHOU
Author Information
1. 深圳市第二人民医院妇科
- Keywords:
microRNA;
cisplatin;
ovarian cancer;
drug resistance
- From:
Journal of Southern Medical University
2015;(1):125-128
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the changes in cisplatin sensitivity of resistant ovarian cancer A2780 cells after inhibition of miR-23a expression and explore the molecular mechanisms. Methods The drug-resistant ovarian cancer A2780 cells were exposed to cisplatin alone or in combination with antagomir-23a. The cell inhibition rates after the treatments were detected using MTT assay, cell cycle changes assessed with flow cytometry, and apoptotic cells observed using Hoechst33258 staining. The changes in glycoprotein P-gp expression in the cells were detected using Western blotting. Results Inhibition of miR-23a combined with cisplatin treatment significantly increased the cell inhibition rate (P<0.01) and lowered the IC50 of cisplatin by 83.76%from 110.18μmol/L in the control group to 17.89μmol/L (P<0.01). The combined treatments also caused cell cycle arrest in G0/G1 phase, increased the cell apoptosis rate (P<0.01) and the number of cells stained with Hoechst33258; the cellular expression of P-gp protein was significantly reduced as the cisplatin doses increased (P<0.01). Conclusion Inhibition of miR-23a expression increases the sensitivity of A2780 cells to cisplatin possibly by inhibiting the negative regulation by miR-23a target genes that causes inhibition of P-gp protein expression.