他莫昔芬与辛伐他汀对人乳腺癌细胞MCF-7的协同效应及机制

目的 探究他莫昔芬(TAM) 与辛伐他汀(SIV) 对人乳腺癌细胞株(MCF-7)的增殖抑制作用及其潜在的作用机制.方法 MTT检测TAM、SIV单独以及联合使用对MCF-7细胞株的增殖抑制作用,计算TAM与SIV单独作用时IC50值以及联合使用时对细胞作用的联合指数(CI),评价两药之间的相互作用.荧光显微镜下观察并拍摄各组中的细胞凋亡形态学变化.流式细胞术检测TAM组、SIV组、TAM+SIV组药物处理后的MCF-7细胞凋亡情况.Western blot法检测各组细胞Bcl-2、Bax的表达情况.结果 MTT法表明,TAM与SIV单药对MCF-7有增殖抑制作用,联合作用时抑制更为明显,且呈协同作用;荧光显微镜及流式细胞术显示TAM与SIV单药对MCF-7有诱导凋亡作用,联合时作用增强;Western blot 法表明TAM+SIV组中Bcl-2表达量较细胞对照组及TAM组、SIV组下降而Bax 表达量增加且更加明显.结论 TAM与SIV联合使用时可显著抑制MCF-7细胞株的增殖,同时可明显诱导MCF-7细胞株凋亡,提示两药联合使用时,乳腺癌患者可能有更好的获益.

Synergistic effect of Tamoxifen and Simvastatin on MCF-7human breast cancer cells and related mechanism

Objective To investigate the synergistic effect of Tamoxifen(TAM) and Simvastatin(SIV) on MCF-7 human breast cancer cells(MCF-7).Methods MTT assay was used to detect antiproliferative effects of TAM,SIV and TAM+SIV on growth of MCF-7 cells.Synergistic interaction between the two drugs was appraised in vitro by using the combination index(CI) method.The cell apoptosis morphological change was detected by the fluorescent microscope.The diversifications of the cell the apoptosis in TAM,SIV and TAM+SIV were analyzed by flow cytometry.The expressions of Bcl-2 and Bax were investigated by Western blot.Results MTT assays indicated that the viability of MCF-7 was markedly reduced when SIV was combined with TAM compared to single drug treatment(CI<1).Furthermore,when SIV in combination with TAM exhibited a synergistic inhibition of proliferation and induction of apoptosis in MCF-7.Moreover, the combination use of TAM and SIV produced a stronger inhibitory effects on Bcl-2 and Bax expression than control or single drug treatment.Conclusion The combination use of TAM and SIV can obviously increase the effect in comparison with single drug treatment,indicating that combination treatment may be a more effective therapy to breast cancer.