MS-275与表阿霉素合用对乳腺癌MCF-7细胞的影响

目的:研究组蛋白去乙酰化酶抑制剂MS-275和表阿霉素联用诱导乳腺癌细胞株MCF-7细胞周期阻滞和细胞凋亡的影响,并对其机制进行初步探讨。方法:体外培养人乳腺癌细胞株MCF-7;应用MTT法检测表阿霉素单用以及和MS-275联用对细胞存活率的影响;应用流式细胞仪检测细胞凋亡率;Western blot分析P21、P53蛋白表达的差异。结果:MS-275和表阿霉素合用较表阿霉素单用能明显降低乳腺癌细胞的存活率,增加细胞的凋亡率,具有剂量的依赖性。单用表阿霉素可以使P21、P53蛋白上调,MS-275和表阿霉素合用较单用两种蛋白上调更加明显。结论:MS-275和表阿霉素合用较单用能增加对乳腺癌细胞MCF-7的细胞毒性。其机制可能和MS-275预处理使染色质的构象发生改变,加强了表阿霉素诱导的P21和P53的表达有关。

Effect of combined MS-275 and Epirubicin on breast cancer cell MCF-7

Objective:To investigate the influence of combined histone deacetylase inhibitor(HDACi) MS-275 and epirubicin induced cell cycle stasis and apoptosis in breast cancer cell line MCF-7,approach thire mechanism.Methods:MCF-7 cells used in the experiment were cultured in vitro. The effect of survival rate on epirubicin alone and associated with MS-275 was measured by MTT .Flow cytometry ( FCM) was used to examine the rate of apoptosis.The difference of P53 and P21 protein was estimated by Western blot.Results:Combining 5-FU and MS-275 not only decreased the survival rate but also increased the apoptosis rate with dose dependent on MCF-7.The levels of P21 and P53 protein were increased when epirubicin was used alone.The combination of two agents increased P21 and P53 protein levels more obviously than epirubicin alone.Conclusion:These results demonstrate that the combination of epirubicin and MS-275 can increase the cytotoxicity of MCF-7 cell line. The effect might be associated with the change of chromatinic conformation which was pretreated by MS-275 and the strengthen of P21 and P53 protein which was induced by epirubicin.