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目的:研究蛋白酶体抑制剂PS341是否可增强他莫昔芬(TAM)诱导的乳腺癌细胞凋亡,并探讨可能的机制。方法:采用MTT方法测定细胞活力,采用流式细胞仪检测细胞凋亡,采用蛋白质印迹法检测Caspase-8的活化,PARP的裂解及死亡受体Fas蛋白的表达。结果:TAM以时间及浓度依赖的方式抑制乳腺癌MCF-7细胞增殖,24及48h的IC50分别为25和6μmol/L,25μmol/L的TAM处理24h可诱导21.9%的MCF-7细胞发生凋亡,10nmol/L的PS341预处理后给予25μmol/L的TAM处理24h细胞凋亡增至34.6%,PS341与TAM均可轻微上调Fas的表达水平,两药联合应用后可显著上调Fas的表达水平,并明显增强线粒体外凋亡通路的活性。结论:PS341与TAM联合应用可通过上调Fas的表达水平,增强TAM诱导的乳腺癌MCF-7细胞凋亡。
AIM: To investigate whether proteasome inhibitor PS341 can enhance the apoptosis of breast cancer cells induced by tamoxifen (TAM) and to explore the possible mechanism. Methods: Cell viability was measured by MTT assay. Apoptosis was detected by flow cytometry. Caspase-8 activation, PARP cleavage and death receptor Fas protein expression were detected by Western blotting. Results: TAM inhibited the proliferation of MCF-7 breast cancer cells in a time-and-concentration-dependent manner. The IC50 values were 25 and 6 μmol / L at 24 and 48 h, respectively. TAM at 25 μmol / L induced 21.9% After treated with 10nmol / L PS341 for 24 hours, apoptosis of cells was increased to 34.6% at 25μmol / L TAM, PS341 and TAM could slightly up-regulate the expression of Fas, and the combination of the two drugs could significantly up-regulate the expression of Fas , And significantly enhanced the mitochondrial apoptotic pathway activity. Conclusion: The combination of PS341 and TAM can enhance the TAM-induced apoptosis of breast cancer MCF-7 cells by up-regulating the expression of Fas.