【摘要】 目的探讨胃肠道癌组织错配修复蛋白表达与其对化疗药物耐药性产生的关系。方法免疫组织(细胞)化学方法检测5例胃癌、18例大肠癌及相应癌旁组织和胃癌细胞株BGC823及其耐药株BGC823/cDDP错配修复蛋白表达情况;MTT法检测癌组织及上述2种细胞株对顺铂、5-Fu、长春新碱、丝裂霉素的耐受性。结果癌组织hMSH2蛋白阳性表达率(74%)与癌旁组织(59%)无显著差别,且在两组表达有显著相关性;癌组织hMLH1蛋白阳性表达率(57%)显著高于癌旁组织(23%)。对5-Fu高度耐药的癌组织错配修复蛋白表达率显著低于中度耐药和不耐药组;癌组织对其他药物耐受程度与错配修复蛋白表达间未见显著相关关系。耐药株hMSH2蛋白表达强度明显弱于亲本株(BGC823),hMLH1蛋白表达强度在2种细胞株无明显差异。耐药株较亲本株对cDDP、5-Fu和VCR耐药性均有增加,耐药指数分别为3.93、1.87和2.03。结论错配修复系统功能状态可能与个体遗传背景有关;其蛋白表达下调参与胃肠道癌对5-Fu的原发耐药机制和胃肠道癌细胞多药耐药性的产生。更多还原

【Abstract】 Objective To investigate the relationship of mismatch repair(MMR) proteins expression to drug resistance of gastrointestinal tract.Methods Immunohistochemistry and immunocytochemistry were used to detect the expressions of hMSH2 and hMLH1 in 5 gastric carcinomas,18 intestinal carcinomas and BGC823,BGC823/cDDP;MTT essay was used to detect the resistance of carcinoma tissues and the cell lines above to cDDP,5-Fu,VCR,MMC.Results The rates of hMSH2 in carcinoma tissues and their surrounding tissues were 74% and 59% respectively.There was no significant difference between them,and it was significantly coincidence between them.The rates of hMLH1 in carcinoma tissues and their surrounding tissues were 57% and 23% respectively.There was significantly difference between them.The rate of MMR protein expression in carcinomas high resistant to 5-Fu was significantly lower than that in carcinomas middle and low resistance to 5-Fu.HMSH2 expression of BGC823/cDDP was weaker than that of BGC823,and the former was more resistant to cDDP, 5-Fu,VCR than the latter.Conclusion The situation of MMR function may be related to individual genetic background and decreasing of MMR protein expression may take part in intrinsic resistance to 5-Fu and multidrug resistance of gastrointestinal carcinomas.更多还原