米非司酮逆转人乳腺癌细胞MCF-7/ADR耐多柔比星机制的探讨  

Reversal effect of mifepristone on human breast cancer cell line MCF-7/ADR

作　　者：黄俊辉[1] 张曦蓓[1] 肖佳[1] 邱霞[1] 刘利[1] 杨国荣[1] 

机构地区：[1]中南大学湘雅医院肿瘤科,湖南长沙410008

出　　处：《实用肿瘤杂志》2011年第6期584-588,共5页Journal of Practical Oncology

基　　金：湖南省科学技术厅科技计划项目(05TH4001)

摘　　要：目的探讨米非司酮对乳腺癌耐药细胞株MCF-7/ADR的逆转耐药作用。方法以亲本乳腺癌细胞MCF-7和耐多柔比星(阿霉素)乳腺癌细胞MCF-7/ADR为研究对象,分别应用MIF进行干预后,流式细胞仪检测MIF作用前后瘤细胞P-gp的表达、细胞内阿霉素蓄积量的变化以及细胞周期的分布。结果 (1)10μmol/L MIF作用72小时后,MCF-7/ADR细胞P-gp表达率[(23.21±1.80)%]明显高于MCF-7细胞[(19.37±2.37)%,P<0.05]。(2)5μmol/L ADR处理后,MCF-7/ADR细胞内ADR蓄积量为(47.13±4.11)%,低于MCF-7细胞[(60.24±2.61)%,P<0.05]。(3)10μmol/L MIF联合5μmol/L ADR处理细胞,MCF-7/ADR和MCF-7细胞内ADR的蓄积量分别为(82.72±2.42)%及(88.63±2.75)%(P>0.05);但均较单用ADR时升高(均P<0.01)。(4)MIF作用前,MCF-7/ADR细胞G0/G1期比例[(77.21±3.10)%]高于MCF-7细胞G0/G1期比例[(59.05±2.16)%,P<0.05];MCF-7/ADR细胞S期比例明显低于MCF-7细胞(P<0.05)。经10μmol/L MIF作用后,MCF-7细胞G0/G1期比例(75.28±2.53)%较MIF作用前明显升高(P<0.05);S期比例则较MIF作用前显著降低(P<0.05);MCF-7/ADR细胞G0/G1期比例和S期比例分别为(80.13±2.72)%及(13.52±1.03)%,与MIF作用前比较差异均无统计学意义(均P>0.05);两种瘤细胞的G2/M期比例与MIF作用无关(P>0.05)。结论 (1)MIF可以逆转MCF-7/ADR的耐药性,其作用机制与降低细胞P-gp含量、增加细胞内ADR蓄积量有关。(2)10μmol/L浓度的MIF对MCF-7/ADR细胞周期分布影响不大。Objective To study the reversal effect of mifepristone on human breast cancer cell line MCF-7/ADR.Methods Both human breast cancer MCF-7 cells and Adriamycin-resistant MCF-7/ADR cells were treated with MIF and adriamycin.Flow cytometry was used to detect the expression of P-gp,the fluorescence storage amount of intracellular ADR and the phase distribution of cell cycle.Results（1） After the treatment of 10μmol/L MIF for 72 hours,the expression rate of P-gp in MCF-7/ADR cells（23.21±1.80） % was higher then that in MCF-7 cells [（19.37±2.37） %,P〈0.05].（2） The fluorescence storage amount of intracellular ADR in MCF-7/ADR was（47.13±4.11） % after treated with 5μmol/L ADR,which was lower than that in MCF-7 [（60.24±2.61） %,P〉0.05].（3） Treated with 10μmol/L MIF and 5μmol/L ADR,the fluorescence storage amount of intracellular ADR in MCF-7/ADR and in MCF-7 was（82.72±2.42） % and（88.63±2.75） % respectively,which were higher than those treated only with ADR（P〈0.01） ,but there was no statistical significance between two kinds of cells（P〈0.05） .（4） Without MIF treatment,the percentage of G0/G1 phase cells in MCF-7/ADR [（77.21±3.10） %] was higher than that in MCF-7 [（59.05±2.16） %,P〈0.05];but the percentage of S phase cells in MCF-7/ADR was significantly lower than that in MCF-7（P〈0.05） .Compared with MCF-7 cells without MIF treatment,in MCF-7 cells treated with 10 μmol/L MIF,the percentage of G0/G1 phase cells [（75.28±2.53） %] was significantly higher（P〈0.05） ,while the percentage of cells at S phase was significantly lower（P〈0.05） .In MCF-7/ADR cells,the percentages of cells at G0/G1 phase and S phase in cells treated with 10 μmol/L MIF were（80.13±2.72） % and（13.52±1.03） %,which were not siginficantly different from the corresponding percentages in cells without MIF treatment（P〉0.05） .The percentage of cells at G2/M phase in both cell types had no correlation with MIF（P〉0.05） .Conclusion（1） MIF can reve

关 键 词：乳腺肿瘤/病理学 乳腺肿瘤/药物作用 表柔比星 米非司酮/投药和剂量 米非司酮/药理学 P糖蛋白 抗药性 肿瘤 细胞周期/药物作用 

分 类 号：R737.9[医药卫生—肿瘤]