米非司酮对宫颈癌亲代和耐药细胞抗肿瘤作用及耐药逆转作用机制的研究

目的探讨米非司酮(RU486)对宫颈癌亲代细胞株(Hela)和耐药细胞株(Hela/MMC)抗肿瘤作用及耐药逆转作用的机制。方法培养Hela细胞及Hela/MMC细胞株后分为4组:空白对照组、单用RU486组、单用MMC组及联用组。采用流式细胞术检测各组细胞周期和细胞凋亡率变化;蛋白印迹法(Western blotting)检测各组p-糖蛋白(p-gp)的表达。结果 (1)Hela细胞及Hela/MMC细胞,单用RU486组较空白对照组G_0/G_1期比例均明显升高,S期比例明显降低,细胞凋亡率明显增高,差异有统计学意义(P<0.05,P<0.01);联用组较单用MMC组G_0/G_1期比例均明显升高,S期比例均明显降低,细胞凋亡率明显增高,差异有统计学意义(P<0.05,P<0.01);(2)Hela/MMC细胞p-gp表达显著高于Hela细胞(P<0.01);Hela/MMC及Hela细胞,其单用RU486组与空白对照组相比,p-gp的表达均显著降低(P<0.05),Hela/MMC细胞系,单用MMC组与空白对照组相比,p-gp的表达无明显变化(P>0.05),在联用组,p-gp的表达显著低于单用MMC组和空白对照组(P<0.01)。结论米非司酮可通过调节细胞周期、促进细胞凋亡、降低p-gp的表达发挥抗肿瘤及耐药逆转作用。

Study on the mechanism of anti-tumor and resistance reversal effect of mifepristone on cervical cancer parental generation and drug resistant cells

Objective To study the mechanism of anti-tumor and reversal effect of mifepristone on cervical cancer parental generation and drug resistant cells.Methods Mifepristone and mitomycin(MMC) respectively and combined effects of Hela cells and Hela/MMC cells,cell cycle and apoptosis rate were detected by flow cytometry.Western blotting detects the expression of p-glycoprotein(p-gp) before and after the influences of mifepristone.Results(1 ) In Hela or Hela/MMC cells,single use mifepristone group,compared with blank control group,the proportion of G_0/G_1 phase was significantly higher, S phase was significantly reduced and cells apoptosis rate was significantly increased,the differences had statistical significance (P <0.05,P < 0.01);In combined use of mifepristone group,compared with single use MMC group,the proportion of G_0/G_1 phase was significantly higher,S phase is significantly reduced and cells apoptosis rate is significandy increased, the differences have statistical significance(P <0.05,P <0.01).(2)The Hela/MMC cell line of p-gp expression was significantly higher than Hela cells(P <0.01);In Hela or Hela/MMC cells,single use mifepristone group,compared with black control group,expression of p-gp were significantly reduced(P <0.05);In Hela/MMC cells,single use MMC group,compared with blank control group,expression of p-gp has no significance(P >0.05);In Hela/MMC cells,in combined use of mifepristone group,expression of p-gp was significantly lower than the single MMC group and blank control group (P <0.01).Conclusion Mifepristone can anti-tumor and reverse drug resistance by regulating the cell cycle,promoting apoptosis rate and reducing the expression of p-gp.