国际肿瘤学杂志

国际肿瘤学杂志 ›› 2018, Vol. 45 ›› Issue (1): 5-.doi: 10.3760/cma.j.issn.1673-422X.2018.01.002

• 论著 • 上一篇    下一篇

白藜芦醇对卵巢癌细胞顺铂化疗的增敏作用

李研   

  1. 056001 河北省邯郸市中心医院妇二科
  • 出版日期:2018-01-08 发布日期:2018-02-12
  • 通讯作者: 李研 E-mail: zxyyliyan@126.com

Effect of resveratrol on cisplatin chemotherapy sensitivity of ovarian cancer cells

Li Yan   

  1. Second Department of Gynecology, Handan Central Hospital of Hebei Province, Handan 056001, China
  • Online:2018-01-08 Published:2018-02-12
  • Contact: Li Yan E-mail: zxyyliyan@126.com

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摘要： 目的研究白藜芦醇对人上皮性卵巢癌SKOV3细胞顺铂化疗敏感性的影响及机制。方法体外培养并取对数生长期人上皮性卵巢癌SKOV3细胞，设空白对照组、白藜芦醇组（20 μg/ml）、顺铂组（40 μg/ml）和联合干预组（白藜芦醇20 μg/ml+顺铂20 μg/ml），每组10个复孔；给药干预48 h后，四甲基偶氮唑蓝（MTT）法测定细胞增殖抑制率，流式细胞术检测细胞周期和细胞凋亡状况，反转录PCR法（RTPCR）检测Bax mRNA、Bcl2 mRNA表达，Western blotting法检测激活型Caspase3蛋白表达。结果联合干预组与顺铂组比较：联合干预组人上皮性卵巢癌SKOV3细胞增殖抑制率［(53.0±8.1)%］显著高于顺铂组［(37.5±6.5)%，P=0.017］，细胞周期G0G1期比例［(61.2±3.4)%］显著高于顺铂组［(54.9±2.8)%，P=0.017］、G2M期比例［(5.1±0.5)%］显著低于顺铂组［(8.6±0.9)%，P=0.008］，细胞凋亡指数［(59.3±7.4)%］显著高于顺铂组［(43.6±6.0)%，P=0.015］，Bax/Bcl2值(4.6±1.8)较顺铂组(3.3±1.4)显著升高（P=0.026），激活型Caspase3蛋白表达（0.47±0.15）较顺铂组（0.38±0.12）显著上调（P=0.011）。白藜芦醇组与空白对照组比较：白藜芦醇组SKOV3细胞周期G0G1期比例［(46.5±2.4)%］显著高于空白对照组［(37.8±1.9)%，P=0.023］，Bcl2 mRNA表达［（32.9±11.2）×10-3］较空白对照组［（44.8±13.0）×10-3］显著下调（P=0.028）、Bax/Bcl2比值（2.1±0.8）较空白对照组（1.5±0.6）显著升高（P=0.019），激活型Caspase3蛋白表达（0.26±0.10）较空白对照组（0.08±0.03）显著上调（P＜0.001）。结论白藜芦醇具有提高人上皮性卵巢癌SKOV3细胞顺铂化疗敏感性的作用，阻滞细胞周期于G0G1期以及调节凋亡相关基因和蛋白表达可能是其重要的分子作用机制。

关键词: 卵巢肿瘤, 顺铂, 药物疗法, 细胞凋亡, 白藜芦醇

Abstract: ObjectiveTo investigate the effect and mechanism of resveratrol on cisplatin chemotherapy sensitivity of human epithelial ovarian cancer SKOV3 cells. MethodsThe 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. ResultsThe 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) ×10-3 vs. (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). ConclusionResveratrol 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