SAHA在Leptin诱导的乳腺癌MCF-7细胞增殖过程中的调控作用  

Regulation of SAHA on cell proliferation induced by leptin in breast cancer cell line MCF-7

作　　者：冯秀艳[1,2] 韩翰[1] 周伟强[1] 

机构地区：[1]沈阳医学院辽宁省环境污染与微生态重点实验室,辽宁沈阳110034 [2]沈阳医学院附属第二医院内分泌科,辽宁沈阳110002

出　　处：《中国药理学通报》2016年第4期503-508,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No81172509);辽宁省教育厅基金资助项目(NoL2012370)

摘　　要：目的为了阐明SAHA调控Leptin诱导的乳腺癌ER+细胞系MCF-7细胞增殖的分子机制,我们采用实时无标记细胞分析系统,动态监测Leptin对MCF-7细胞生长状况的影响。方法通过自动细胞分析仪Muse Cell Analyzer分析Leptin和SAHA对MCF-7细胞活力、细胞凋亡以及细胞周期产生的影响,并应用细胞凋亡抗体芯片测定Leptin和SAHA两种处理因素作用MCF-7细胞后相关凋亡通路分子表达变化的情况。结果低浓度Leptin对MCF-7细胞生长有诱导作用,其浓度为0.625 nmol·L^(-1)时作用效果最明显。细胞分析结果表明,SAHA能明显抑制Leptin诱导的MCF-7细胞增殖,经SAHA处理后MCF-7细胞活力明显下降,细胞凋亡率明显增多,细胞被大量阻滞于G_0/G_1期。凋亡抗体芯片筛查结果发现,SAHA可明显诱导MCF-7细胞内促凋亡因子Bax、Caspase-3的表达,并且与凋亡产生密切相关的TRAIL DR5、p21^(CIP1)蛋白的表达也明显上升,Claspin、Clusterin、XIAP、Survivin蛋白的表达明显下降,而Leptin对上述蛋白的表达具有相反作用。结论 Leptin、SAHA对乳腺癌ER^+细胞MCF-7的影响可能与乳腺癌细胞内凋亡通路激活有关,特别是与内源性线粒体凋亡通路引发的Caspase-3释放密切相关。To clarify the molecular mechanism of SAHA in the cell proliferation of ER-positive breast cancer cell line MCF-7 induced by leptin. Methods Human breast cancer cell MCF-7 was incubated with SAHA and / or leptin,and cell viability,apoptosis and cell cycle of MCF-7 cells were detected by Muse Cell Analyzer. The expression of proteins related with apoptosis was determined by apotosis antibody array. Results Real-time cell proliferation assays indicated that the induction effect of leptin for MCF-7 cells reached the peak at a concentration of 0. 625 nmol · L^(-1). SAHA reduced the viability of MCF-7 cells,induced G_0/ G_1 phase arrest in the cell cycle,and triggered the apoptosis. Meanwhile,SAHA significantly induced the protein expressions of some apoptotic factors,including Bax,Caspase-3,TRAIL DR5,p21^(CIP1),and inhibited the expressions of Claspin,Clusterin,x-linked inhibitor of apoptosis protein( XIAP) and survivin. However,leptin had reverse effects on the related expression of the proteins. Conclusion The effects of cell proliferation by leptin and SAHA treatment in breast cancer ER positive cell line MCF-7 may involve in the activation of apoptosis pathway,in particular with releasing of Caspase-3 trigged by endogenous mitochondrial apoptosis pathway.

关 键 词：细胞凋亡 乳腺癌 雌激素受体阳性细胞 MCF-7 SAHA 瘦素 

分 类 号：R329.24[医药卫生—人体解剖和组织胚胎学] R329.25[医药卫生—基础医学]