Molecular mechanism of increased sensitivity of cisplatin to ovarian cancer by inhibition of microRNA-23a expression.

OBJECTIVE: The aim of this study is to investigate the sensitivity change and the preliminary mechanism of ovarian cancer cells on the resistant to chemotherapeutic drugs by inhibiting miR-23a expression. METHODS: The ovarian cancer cell lines A2780 was administrated with antagomir-23a and platinum, and then the cell proliferation inhibition rate was determined by MTT assay. The cell cycle distribution was detected by flow cytometric analysis. The apoptotic morphological changes were analyzed by Hoechst33258 staining. The glycoprotein P-gp expression changes were detected by Western blot analysis. RESULTS: The cell proliferation inhibition rate increased significantly after the administration of miR-23a and platinum (P<0.01). The middle concentration of drug efficacy IC50 in experimental group decreased by 83.76% compared with that in control group, which was 17.89 µmol/L vs 110.18 µmol/L (P<0.01). The cell lines A2780 were arrested in G0/G1 phase and apoptosis rate kept increasing (P<0.05). The cell nuclei stained by Hoechst33258 were obviously enhanced and demonstrated apoptosis morphology, such as condense, pyknosis. Compared with control group, the levels of P-gp protein expression in experimental group decreased along with the increase of the cisplatin concentration (P<0.05). CONCLUSION: The inhibition of miR-23a expression could significantly increase the sensitivity of cisplatin towards tumor cells, and it was probably because the negative regulatory factors of miR-23a target genes was released, and as a result, the expression of P-gp protein was inhibited.

[Inhibition of microRNA-23a increases cisplatin sensitivity of ovarian cancer cells: the possible molecular mechanisms].

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-23 a combined with cisplatin treatment significantly increased the cell inhibition rate (P<0.01) and lowered the IC(50) so of cisplatin by 83.76% from 110.18 µmol/L in the control group to 17.89 µmol/L (P<0.01). The combined treatments also caused cell cycle arrestin 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.