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

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)10 μmol/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)5 μmol/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) 10 μmol/L MIF联合5 μmol/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10 μmol/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) 10 μmol/L浓度的MIF对MCF-7/ADR细胞周期分布影响不大.

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

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 reverse the drug resistance of MCF-7/ADR through reducing the expression of P-gp and increasing the accumulation of intracellular ADR.(2) 10 μmol/L mifepristone has no distinct influence on the phase distribution of cell cycle in breast cancer cell line MCF-7/ADR.