抑制STAT5a、STAT5b对大肠癌细胞增殖、周期和凋亡的影响  

Inhibition of STAT5a and STAT5b effect cell poliferation, cell cycle and apoptosis on human colorectal cancer

作　　者：杜婉[1] 熊华[1] 房静远[1] 

机构地区：[1]上海交通大学医学院附属仁济医院消化科上海市消化疾病研究所,上海200001

出　　处：《世界最新医学信息文摘》2012年第2期19-24,共6页World Latest Medicine Information Electronic Version

基　　金：高等学校博士学科点专项科研基金资助课题（200802480067）

摘　　要：分析和探讨信号转导与激活因子STAT5的两个亚型STAT5a、STAT5b对大肠癌细胞增殖、周期及凋亡的影响。方法培养大肠癌细胞SW1116和LoVo，分别瞬时转染小干扰RNA静默STAT5a、STAT5b。CCK8试剂盒检测细胞增殖情况；同时以流式细胞仪分析SW1116和LoVo细胞周期；AnnexinV／PI染色检测凋亡；提取细胞蛋白，Western blot检测下游周期相关蛋白（p16[NK4A和p27kip1）和凋亡相关蛋白（BCL-2和survivin）的表达变化。结果大肠癌细胞SW1116和LoVo静默STAT5a和STAT5b后，细胞增殖能力明显降低，细胞发生G1期阻滞，并且发生凋亡。周期相关蛋白p161NK4A和p27kip1明显增高，凋亡相关蛋白BCL-2、survivin明显降低。并且，STATSb对大肠癌增殖凋亡的影响比STAT5a明显，STAT5a与STAT5b对大肠转移癌LoVo的影响比大肠原位癌SW1116明显。结论抑制STAT5两亚型可通过调节下游周期及凋亡相关蛋白的表达从而降低结肠癌细胞的增殖能力。PURPOSE： To investigate the role of two isoforms of STAT5 in the progression of colorectal cancer （CRC）. METHODS： We studied cell viability using Cell Counting Kit 8 with depletion of each STAT5a/5b, which was induced by treating CRC cells with the respective small interfering RNA （siRNA）. Cell cycle and apoptosis was determined by flow cytometry analysis with RNAi-induced deficiency of STAT5a/5b. Besides, the expression of cell-cycle-regulatory and apoptosis proteins that are known to be downstream targets of the STATs pathway was examined. RESULTS： Our results showed that both STAT5a and STAT5b are involved in the cell growth, cell-cycle progression, and apoptosis of CRC cells. Upregulation of p 16ink4a and p27kipl expression and down- regulation of Bcl-2 and survivin expression exerted their effects after targets of the STAT5 isoforms. We found that STAT5b induced cell apoptosis to greater extent than STAT5a and STAT5a/b played more important roles in LoVo cells than in SW1116 cells. CONCLUTIONS： Both the isoforms of STAT5 are involved in the growth and cell-cycle progression of CRC cells via downstream targets of the STATs pathway, and they could play a more important role in the progression of metastatic adenocarcinoma.

关 键 词：大肠癌 STAT5a STAT5B 周期阻滞 凋亡 

分 类 号：R735.3[医药卫生—肿瘤]