Effect of resveratrol on cisplatin chemotherapy sensitivity of ovarian cancer cells

Abstract

Objective To investigate the effect and mechanism of resveratrol on cisplatin chemotherapy sensitivity of human epithelial ovarian cancer SKOV3 cells. Methods The cultured in vitro human ovarian cancer SKOV3 cells in logarithmic growth phase were treated with resveratrol (20 μg/ml), cisplatin (40 μg/ml) and resveratrol (20 μg/ml) + cisplatin (20 μg/ml) respectively, and the blank group was set, n=10. After 48 hours, the cellular growth inhibition rate was calculated by methyl thiazolyl thiazolium (MTT), cell cycle and apoptosis rate were analyzed by flow cytometry, the expressions of Bax mRNA and Bcl-2 mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR), and the expression of cleaved Caspase-3 protein was detected by Western blotting. Results The cellular growth inhibition rate of SKOV3 cells in resveratrol + cisplatin group was significantly increased than that in cisplatin group [(53.0±8.1)% vs. (37.5±6.5)%, P=0.017], the proportion of G0-G1 phase cells in resveratrol + cisplatin group was significantly higher than that in cisplatin group [(61.2±3.4)% vs. (54.9±2.8)%, P=0.017], the proportion of G2-M phase cells in resveratrol + cisplatin group was significantly lower than that in cisplatin group [(5.1±0.5)% vs. (8.6±0.9)%, P=0.008], the apoptosis index in resveratrol + cisplatin group was significantly increased than that in cisplatin group [(59.3±7.4)% vs. (43.6±6.0)%, P=0.015], the ratio of Bax/Bcl-2 in resveratrol + cisplatin group was significantly increased than that in cisplatin group (4.6±1.8 vs. 3.3±1.4, P=0.026), and the expression of cleaved Caspase-3 protein in resveratrol + cisplatin group was significantly increased than that in cisplatin group (0.47±0.15 vs. 0.38±0.12, P=0.011). Compared with blank group, the G0-G1 phase in cell cycle of resveratrol group was significantly increased [(46.5±2.4)% vs. (37.8±1.9)%, P=0.023], the expression of Bcl-2 mRNA was significantly decreased [(32.9±11.2) ×10-3vs. (44.8±13.0)×10-3,P=0.028], the ratio of Bax/Bcl-2 was significantly increased (2.1±0.8 vs. 1.5±0.6, P=0.019), and the expression of cleaved Caspase-3 protein was significantly increased (0.26±0.10 vs. 0.08±0.03, P<0.001). Conclusion Resveratrol can effectively enhance the effect on human epithelial ovarian cancer SKOV3 cells treated by cisplatin, which is perhaps related to its effects of blocking the cell cycle G0-G1 and altering the expression of apoptosis-related genes and proteins. Key words: Ovarian neoplasms; Cisplatin; Drug therapy; Apoptosis; Resveratrol