Psammaplysene A诱导的叉头转录因子O1A蛋白表达对乳腺癌细胞增殖凋亡的影响  

Effects of psammaplysene A induced forkhead transcription factors O1A expression in cell proliferation and apoptosis of human breast carcinoma cell lines

作　　者：胡建莉[1] 吴边[1] 屈新才[2] 

机构地区：[1]华中科技大学同济医学院附属协和医院肿瘤中心,武汉430022 [2]华中科技大学同济医学院乳腺外科,武汉430022

出　　处：《中华实验外科杂志》2013年第10期2092-2094,共3页Chinese Journal of Experimental Surgery

基　　金：湖北省自然科学基金资助项目（2012FFB02419）

摘　　要：目的 探讨Psammaplysene A（PsA）诱导叉头转录因子O1A蛋白（FOXO1A）表达对人乳腺癌细胞株MCF-7及SKBR3增殖和凋亡的影响.方法 用PsA干预2株细胞后,激光共聚焦显微镜（CSM）观察FOXO1A蛋白在细胞中表达；噻唑蓝（MTT）法检测细胞增殖；流式细胞仪（FCM）分析细胞凋亡和周期变化；Western blot检测B细胞淋巴瘤/白血病-2蛋白家族促凋亡调节蛋白（Bim）表达.结果 FOXO 1A蛋白定位于胞核中,PsA诱导后其表达明显增加,细胞发生凋亡,生长减慢.分别用0.1 μmol/L和1.0 μmol/L的PsA干预2株细胞后,凋亡率分别为（16.3±1.4）％和（32.5±2.3）％；（13.7±1.9）％和（30.3±1.6）％；Bim蛋白增加,和阴性对照组比较差异有统计学意义（P＜0.01）.结论 PsA通过诱导FOXO1A蛋白表达抑制了乳腺癌细胞增殖,促进凋亡,其机制可能与Bim蛋白激活有关.FOXO1A基因有望成为乳腺癌基因治疗的有效靶点.Objective To investigate the effects of psammaplysene A （PsA） induced forkhead transcription factors O1 A （FOXO1 A） expression in cell proliferation and apoptosis of human breast carcinoma cell lines.Methods Breast carcinoma cells were treated by PsA.Localization of FOXO1 A protein was analyzed by laser scanning confocal microscopy （CSM）.Cell proliferation was evaluated by methyl thiazol tetrazolium （MTT） assay.Cell apoptosis was detected by flow cytometry （FCM）.Expression of B-cell lymphoma/Leukemia-2 interacting mediator of cell death （Bim） and FOXO1A were detected by Western blot.Results FOXO1A protein located in cell nucleus,and FOXO1A expression level increased after PsA treatment.Cell viability significantly decreased in MCF-7 and SKBR3 cells.Apoptosis rate of MCF-7 and SKBR3 cellwas （16.3±1.4）％ and （32.5±2.3）,（13.7±1.9）％ and （30.3±1.6）％ when exposed to 0.1,1 μmol/L PsA respectively.Meanwhile,protein levels of Bim and FOXO1A significantly increased comnpared to phosphate buffer （PBS） negative control of MCF-7 and SKBR3 cells （P ＜0.01）.Conclusion Increase of FOXO1A expression after PsA treatment could inhibit proliferation and induce apoptosis in breast cancer cells.The possible mechanism relates to Bim activation induced by FOXO1A.FOXO1A gene is a promising target for gene therapy against breast cancer.

关 键 词：乳腺肿瘤 Psammaplysene A 叉头转录因子O1A蛋白 

分 类 号：R737.9[医药卫生—肿瘤]