塞来昔布对大肠癌细胞株HT-29增殖和凋亡的影响(英文)  

Effects of Celecoxib on cell proliferation and apoptosis in human colorectal cancer cell line HT-29

作　　者：彭杰[1] 张桂英[1] 肖志强[1] 

机构地区：[1]中南大学湘雅医院消化内科,湖南长沙410008

出　　处：《中国现代医学杂志》2004年第21期30-34,共5页China Journal of Modern Medicine

基　　金：Project supported by National Natural Science Foundation of China;No30271516;andFoundation from Science and technology Bureau of Hunan;No03SSY4080.30

摘　　要：目的体外观察塞来昔布对大肠癌细胞株HT-29细胞增殖和凋亡的影响,探讨其可能的作用机制。方法采用噻唑蓝(MTT)比色法,流式细胞(FCM)、吖啶橙/溴化乙啶染色结合荧光显微镜、Western印迹法等技术,研究塞来昔布对HT-29细胞增殖的抑制和可能的机制。结果塞来昔布抑制HT-29细胞生长,呈浓度和时间依赖性。流式术检测出典型的亚二倍体“凋亡峰”,凋亡率(7.31±2.37)%^(48.30±2.86)%;使G0/G1期细胞比例升高,S期和G2/M期比例缩小、细胞核固缩、凋亡小体形成等。凋亡比例呈剂量和时间依赖。塞来昔布降低细胞周期素依赖蛋白激酶CDK2和CDK4的表达、上调细胞周期素依赖蛋白激酶抑制因子P21WAF1/CIP1n蛋白表达。结论体外塞来昔布抑制HT-29细胞增殖,并诱导细胞凋亡;下调CDK_2和CDK_4蛋白表达,上调P21WAF1/CIP1n蛋白表达。塞来昔布抑制HT-29细胞增殖、诱导凋亡可能与阻止细胞周期进展有关。Objective:To study the effect of Celecoxib on cell proliferation and apoptosis of human colorectal cancer cell line HT-29and the probable mechanism involved.Methods:Using MTT assay,flow cytometry(FCM),Acridine orange and Ethidium bromide staining under fluorescence microscope,Western blotting,the effect of Cele-coxib on the HT-29of proliferation and related mechanism were studied.Results:The growth of HT-29was inhib-ited by Celecoxib in a dose-and time-dependent manner.Sub-G 1 peak was detected by FCM,and the apoptotic rate was between(7.31±2.37)%and(48.30±2.86)%.The cell ratios of G 0 /G 1 increased,whereas the cell ratios of S and G 2 /M phase decreased after treatment and was in a dose-dependent manner.The HT-29cell line exhibited some morphologie feature of apoptosis,including cell shrinkage,nuclear condensation,DNA fragmentation,and for-mation of apoptosis bodies,and apoptotic index was in a dose-and time-dependent manner under Acridine orange and Ethidium bromide staining.Celecoxib down-regulated the expressions of CDK 2 ,CDK 4 proteins and up-regulated the expression of P 21WAF1/CIP1 protein.Conclusions:Celecoxib inhibits proliferation and inducs apoptosis of human col-orectal cancer cell line HT-29,down-regulats the expressions of CDK 2 ,CDK 4 proteins and up-regulats the expres-sion of P 21WAF1/CIP1 protein.The effect of Celecoxib on phase of cell cycle may be partially explained as the cytotoxic effects of Celecoxib.

关 键 词：塞来昔布 HT-29细胞系 细胞增殖 细胞凋亡 细胞周期 CDK2 CDK4 P21^WAF1/CIP1n 

分 类 号：R735.3[医药卫生—肿瘤]