Nimesulide诱导胃癌细胞凋亡的作用机制研究  

A study on the mechanisms of apoptosis of gastric cancer line induced by Nimesulide

作　　者：宋军[1] 钱伟[1] 侯晓华[1] 

机构地区：[1]华中科技大学同济医学院协和医院消化科,武汉430022

出　　处：《中华消化杂志》2002年第12期722-725,共4页Chinese Journal of Digestion

摘　　要：目的　非甾体抗炎药诱导胃癌细胞凋亡的机制不清楚。通过研究选择性COX 2抑制剂Nimesulide对人胃癌细胞系SGC 790 1的COX 2mRNA表达和c myc、Bcl 2、caspase 3凋亡基因蛋白表达的影响 ,探索其诱导胃癌细胞凋亡的机制。方法　胃癌细胞的凋亡用电子显微镜、AnnexinV FITC染色、流式细胞仪技术测定。COX 2基因表达用RT PCR法测定。c myc、Bcl 2和caspase 3蛋白表达用免疫细胞化学技术测定。结果　Nimesulide在浓度为 50 μmol/L时作用 48、72h和浓度为 1 0 0和2 0 0 μmol/L 时作用 2 4、48、72h均可诱导胃癌细胞凋亡 ,凋亡率分别为 7.51 % ,9.86 % ;1 1 .58% ,1 2 .45 % ,1 6 .66 %和 1 2 .2 1 % ,1 5 .38% ,2 0 .2 8% ,呈浓度和时间依赖性。Nimesulide可降低COX 2mRNA表达和Bcl 2蛋白表达 ,增加c myc和caspase 3蛋白表达。 2 0 0 μmol/LNimesulide作用 72h ,Bcl 2 ,c myc和caspase 3蛋白表达阳性率分别为 (2 0 .2± 7.6) % ,(49.2± 1 5 .1 ) %和 (34 .6± 1 2 .9) % ,对照组为(44.6± 1 2 .1 ) % ,(2 4 .7± 9.5) %和 (1 4 .8± 6 .4) % ,三者对照比较 ,差异有显著性 (P <0 .0 1。)结论　Nimesulide可诱导胃癌细胞SGC 790 1凋亡 ,其机制涉及Bcl 2表达下调、c myc表达上调及caspase 3激活。Objective Non steroidal anti inflammatory drugs(NSAIDs)can induce apoptosis in gastric cancer cell and the mechanism is not clear. We aimed to study the mechanism of selective COX 2 inhibitor Nimesulide induced apoptosis of human gastric cancer line SGC 7901 by detecting the expressions of COX 2 at mRNA level, c myc, Bcl 2 and caspase 3 at protein level. Methods Apoptosis was determined by electronic microscopy, Annexin V FITC staining and flow cytometry. The mRNA of COX 2 was detected by RT PCR. The protein expressions of c myc, Bcl 2 and caspase 3 were examined by immunohistochemistry. Results Nimesulide of 50 μmol/L at 48 and 72 h, and of 100 μmol/L and 200 μmol/L at 24, 48 and 72 h induced apoptosis of gastric cancer cells in a dose and time dependent manner.Their apoptotic rates were 7.51%, 9.86% and 11.58%, 12.45%, 16.66% and 12.21%, 15.38%, 20.28% respectively. It increased c myc and caspase 3 expression and decreased Bcl 2 expression and COX 2 mRNA expression. The positive protein expression rates of Bcl 2, c myc and capase 3 were (20.2±7.6)%,(49.2±15.1)% and (34.6±12.9)% respectively with Nimesulide of 200 μmol/L at 72 h,while the controls being (44.6±12.1)%, (24.7 ±9.5)% and (14.8±6.4)% the three comparative P <0.01.Conclusions Nimesulide can induce apoptosis in gastric cancer line SGC 7901 by upregulation of c myc expression, downregulation of Bcl 2 expression and activation of caspase 3.

关 键 词：NIMESULIDE 胃癌 细胞凋亡 作用机制 

分 类 号：R735.2[医药卫生—肿瘤]