西咪替丁对胃癌细胞SGC-7901增殖及凋亡的影响  

Effect of cimetidine on the proliferation and apoptosis of human gastric cancer cell line SGC-7901

作　　者：姜成钢[1] 李嘉斌[2] 徐惠绵[1] 于淼[1] 吴涛[1] 刘芙蓉[2] 

机构地区：[1]中国医科大学附属第一医院肿瘤外科,辽宁省沈阳市110001 [2]中国医科大学细胞生物学教研室,辽宁省沈阳市110001

出　　处：《世界华人消化杂志》2007年第2期118-122,共5页World Chinese Journal of Digestology

摘　　要：目的:观察西咪替丁对人胃癌SGC-7901细胞增殖、细胞周期分布及凋亡的影响,并初步探讨其作用机制.方法:培养人胃癌SGC-7901细胞,以不同浓度的西咪替丁处理后用MTT法检测SGC-7901细胞的增殖情况;流式细胞术检测癌细胞周期和凋亡;Hoechst33258染色后荧光显微镜观察药物作用后癌细胞的形态变化;透射电镜观察用药后细胞超微结构的改变;Western印记法检测Bcl-2和Bax蛋白表达.结果:以不同浓度的西咪替丁分别处理人胃癌SGC-7901细胞24h和48 h,结果发现,在0.5,1,2.5,5,10 mmol/L时对SGC-7901细胞的增殖具有显著的抑制作用,与对照组相比差异显著(24 h:0.705±0.018,0.560±0.038,0.408±0.029,0.276±0.042,0.205±0.031 vs 0.803±0.012,P<0.05;48 h:0.902±0.024,0.671±0.015,0.420±0.030,0.180±0.037,0.0117±0.021 vs 1.079±0.040,P<0.05),并呈时间和剂量依懒性,而在0.25 mmol/L以下浓度对SGC-7901细胞未见明显细胞毒作用;0.5-10 mmol/L西咪替丁作用后,可观察到典型的细胞凋亡形态学改变;流式细胞仪检测可见凋亡峰,G0/G1期细胞明显增多(60.83±2.27,67.21±1.18,75.15±4.01,81.88±3.10,86.99±1.43 vs 50.28±1.97,P<0.05);西咪替丁还可下调SGC-7901细胞中的Bcl-2蛋白表达,上调Bax蛋白表达.结论:西咪替丁可改变细胞周期分布,并能通过下调Bcl-2、上调Bax蛋白表达,诱导SGC-7901细胞凋亡,从而抑制细胞增殖.AIM： To investigate the effect of cimetidine on the proliferation and apoptosis of human gastric cancer cell line SGC-7901 and its related mechanism. METHODS： Human gastric cancer cell SGC-7901 was cultivated by routine method, then treated with different concentrations of cimetidine. The proliferation of SGC-7901 cells was examined by MTr assay, and the cell cycle and apoptosis were detected by flow cytometry. After Hoechst33258 staining, the morphologic changes of SGC-7901 cells were observed under fluorescence microscope, and the ultrastructure of the cells was investigated by transmission electron microscopy. The levels of Bcl-2 and Bax protein expression were detected by Westem blot analysis. RESULTS： After dealing with cimetidine （0.5, 1, 2.5, 5, 10 mmol/L） for 24 and 48 hours, we found that cimetidine significantly inhibited the proliferation of SGC-7901 cells in a time- and concentration-dependent manner （24 h： 0.705 ± 0.018, 0.560 ± 0.038, 0.408 ± 0.029, 0.276 ± 0.042, 0.205 ± 0.031 vs 0.803 ± 0.012, P 〈 0.05; 48 h： 0.902 ± 0.024, 0.671 ± 0.015, 0.420 ±0.030, 0.180 ± 0.037, 0.117 ± 0.021 vs 1.079 ± 0.040, P 〈 0.05）, whereas there was no significant cytotoxic effect as the concentration was below 0.25 mmol/L, cimetidine at the concentrations of 0.5, 1, 2.5, 5, and 10 mmol/L induced typical apoptosis of SGC-7901 cells, and flow cytometry showed an apoptosis peak. The percentage of G0/G1-phase cells was significantly increased （60.83% ± 2.27%, 67.21% ± 1.18%, 75.15% ± 4.01%, 81.88% ± 3.10%, 86.99% ± 1.43% vs 50.28% ± 1.97%, P 〈 0.05）. The expression of Bcl-2 protein was decreased while that of Bax protein was increased following cimetidine treatment. CONCLUSION： Cimetidine may inhibit the proliferation of SGC-7901 cells through inducing cell apoptosis and cell cycle arrest.

关 键 词：胃肿瘤 西咪替丁 凋亡 细胞周期 

分 类 号：R735.2[医药卫生—肿瘤]