丝裂霉素联合舒林酸对胃癌SGC7901细胞诱导凋亡的研究  

Apoptosis induced by mitomycin with sulindac on human gastric cancer cell SGC7901

作　　者：颉永乐[1] 马力[1] 

机构地区：[1]兰州医学院附属二院消化内科,甘肃省兰州市730030

出　　处：《世界华人消化杂志》2004年第3期542-545,共4页World Chinese Journal of Digestology

摘　　要：目的:研究丝裂霉素与舒林酸合用对人胃腺癌SGC7901细胞的生长抑制、诱导凋亡及凋亡相关基因bcl-2和COX-2 基因表达的影响. 方法:SGC7901胃癌细胞被分为三个实验组,舒林酸组、丝裂霉素组和舒林酸与丝裂霉素联合组.应用光镜、激光共焦显微镜、MTT法、流式细胞仪和免疫组化技术研究三组药物作用后,胃癌细胞的形态学变化、生长抑制、诱导凋亡和对凋亡相关基因Bcl-2和COX-2表达的影响. 结果:药物作用于细胞后,可看到较为典型的细胞凋亡形态学变化:细胞核固缩,染色质凝集,核碎裂,染色质片段化,凋亡小体形成等.药物干预24 h,联合组和MMC组对胃癌SGC7901细胞诱导的凋亡率分别为12.0%和7.20%. 对细胞的增生抑制以联合组最强,MMC次之,舒林酸最弱. 经MMC作用24h后,COX-2和Bcl-2蛋白表达增强,而联合组出现COX-2蛋白表达减弱,Bcl-2蛋白亦未出现明显升高. 结论:人胃癌SGC7901细胞体外实验中,MMC联合舒林酸使用,可使增生抑制加强.MMC可能由于上调COX-2、Bcl-2蛋白,减弱了自身对SGC7901胃癌细胞的诱导凋亡, MMC联合舒林酸可抑制COX-2、Bcl-2表达,从而提高MMC的抗癌效果.AIM: To investigate the effects of mitomycin (MMC) with sulindac on the cell viability, apoptotic induction and expression of apoptosis-related gene Bcl-2 and cyclooxygenase-2 (COX-2) in gastric adenocarcinoma cell SGC7901. METHODS: Human gastric cancer SGC7901 cells were divided into three groups, sulindac, MMC and sulindac with MMC. After treatment with drugs, cell viability was examined by MTT assay. Flow cytometry was used for the cell cycle distribution and apoptotic rates. The morphology of the cells was observed under light microscope and interactive laser cytometer. The expression of COX-2, Bcl-2 was determined by the immunocytochemical method. RESULTS: After exposure for 12 h to three kinds of drugs, gastric cancer cells SGC7901 presented some morphologic features of apoptosis, including cell shrinkage, nuclear condensation, DNA fragmentation, formation of apoptotic bodies. The effects of growth inhibition were more obvious in cotreatment group with MMC and sulindac than MMC group. The apoptotic rates in cotreated cells and MMC-treated cells at 24 h after treatment were 12.0% and 7.2%, respectively. After exposure for 24 h to MMC, upregulation of COX-2 and Bcl-2 protein expression was noted, meanwhile, in cotreatment group, the levels of COX-2 were downregulated but the expression of Bcl-2 gene was not changed significantly. CONCLUSION: MMC-induced apoptosis is reduced by upregulating the expression of COX-2 and Bcl-2 genes. MMC combined with sulindac can suppress growth of gastric cancer cells through induction of apoptosis which may be mediated by downregulation of apoptosis-related Bcl-2 gene and COX-2 gene.

关 键 词：丝裂霉素 舒林酸 胃癌 SGC7901细胞 诱导凋亡 联合化疗 COX-2蛋白 Bcl-2蛋白 

分 类 号：R735.2[医药卫生—肿瘤] R730.53[医药卫生—临床医学]