非甾体类抗炎药对MKN-45细胞影响的研究

The study of the effects on MKN-45 after the treatment of non-steroidal anti-inflammatory drugs

目的 :观察 3种非甾体类抗炎药 (non -steroidalanti -inflammatorydrugs ,NSAIDs)阿司匹林、消炎痛、NS - 398对人胃低分化腺癌细胞株MKN - 45的影响 ,探讨非甾体类抗炎药治疗胃癌的可能机制。方法 :采用生长曲线、细胞毒性试验、光镜、电镜、免疫细胞化学等技术 ,研究NSAIDs对胃癌细胞MKN - 45的增殖抑制、形态学变化以及对COX - 1 ,2、hMLH1、hMSH2的影响。结果 :不同NSAIDs对细胞生长的抑制作用不同 ,NS - 398的抑制作用最强。阿司匹林、消炎痛、NS - 398对MKN - 45细胞的IC5 0值分别约为 6 0 0 μmol/L、80 μmol/L、5 0 μmol/L。扫描电镜检查发现MKN - 45细胞表面的分泌泡有脱失现象。免疫细胞化学研究发现正常MKN - 45细胞COX - 2、hMLH1、hMSH2表达 ,COX - 1不表达。 30 μmol/LNS - 398作用于MKN - 45细胞后COX - 2表达缺失。 结论 :NSAIDs抑制MKN - 45细胞生长 ,对细胞有毒性作用 ;COX - 2选择性抑制剂NS - 398在一定浓度可以抑制COX - 2表达 ,对治疗胃癌有一定作用。

Objective: To investigate the effects on human gastric adenocarcinomal poorly differentiations cell line MKN-45 of 3 kinds of NSAIDs,aspirin,indomethacin and NS-398,and to explore the possible mechanism of NSAIDs for gastric carcinoma.Methods:Cell proliferation ability of gastric cancer cell MKN-45 treated by NSAIDs was examined by using growth curve. The cytotoxicity of NSAIDs on MKN-45 cells was determined by using MTT assay. The morphologic changes of MKN-45 cells was examined by microscope and electron microscope .The expression of COX-1,2?hMLH1?hMSH2 were studied with immunocytochemical method.Result:NSAIDs significantly inhibited the growth of MKN-45. NSAIDs had remarkable cytotoxic effect on MKN-45.The IC50 of aspirin was 600μmol/L,indomethacin was 80μmol/L and NS-398 was 50μmol/L respectively. Normal MKN-45 cells exhibited COX-2, hMLH1 and hMSH2 expression,while COX-1 not.After the treatment of 30μmol/L NS-398, COX-2 expression was absent.Conclusion: NSAIDs inhibited the growth of MKN-45 ,and had cytotoxic effect on MKN-45; COX-2 selective inhibitor NS-398 could inhibit the expression of COX-2 in a certain concentration,and had effect on gastric carcinoma therapy.