PS341对他莫昔芬诱导乳腺癌MCF-7细胞凋亡影响及其机制的探讨  

Effect and mechanism of PS341 on tamoxifen-induced breast cancer MCF-7 cells apoptosis

作　　者：闫顺朝[1] 张凌云[1] 曲秀娟[1] 焦昕[2] 侯柯佐[1] 滕月娥[1] 刘云鹏[1] 

机构地区：[1]中国医科大学附属第一医院肿瘤内科,辽宁沈阳110001 [2]沈阳市胸科医院呼吸内科,辽宁沈阳110044

出　　处：《中华肿瘤防治杂志》2012年第10期731-734,共4页Chinese Journal of Cancer Prevention and Treatment

基　　金：国家自然科学基金(81172198;81172535);辽宁省教育厅课题(L2010698);辽宁省教育厅实验室项目(LS2010169);辽宁省科技厅(2010225032)

摘　　要：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。OBJECTIVE：To investigate the effect of PS341 on tamoxifen-induced apoptosis,and explore the possible mechanism. METHODS： Cells proliferation was measured using MTT assay. Cells apoptosis was determined by flow cytometry. Expression of protein was analyzed by western blot. RESULTS： TAM triggered a time and dose-dependent inhibition of MCF-7 cells proliferation. The 50% inhibitory concentrations （IC50） at 24 h and 48 h were 25 μmol/L and 6 μmol/L respectively. TAM concentration up to 25μmol/L induced about 21. 9%o cells apoptosis. Pretreating with 10 nmol/L PS341 enhanced tamoxifen-induced apoptosis from 21. 9% to 34. 6%. Western blot analysis showed that tamoxifen or PS341 alone induced only a modest upregulation of Fas. PS341 combined with tamoxifen significantly upregulated the expression of Fas and enhanced the activation of extrinsic apoptosis pathway. CONCLUSION： PS341 can en hanced tamoxifen-induced breast cancer MCF-7 cells apoptosis through upregulating the expression of Fas.

关 键 词：乳腺肿瘤 PS341 他莫昔芬 凋亡 

分 类 号：R737.9[医药卫生—肿瘤]