【摘要】 【目的】探讨切割修复交叉互补基因 2 (excisionrepaircross complementingrodentrepairdeficiencygene 2 ,ERCC2 )表达与人肿瘤对抗癌药耐药的关系。【方法】采用Westernblot检测美国国家癌症研究所 (NationalCancerInstitute,NCI)用于抗癌药筛选的 6 0株人肿瘤细胞的ERCC2表达 ,并与 170种抗癌药物的细胞毒试验结果进行相关性分析。【结果】肿瘤细胞ERCC2的蛋白表达水平高低不一 ,其中 6株细胞的ERCC2蛋白水平在可测定范围以下。 170种抗癌药物中有 2 8种化疗药物的耐药性与肿瘤细胞的ERCC2蛋白水平相关性显著或非常显著。根据药物作用机理分析 ,肿瘤细胞ERCC2表达与其对烷化剂和抗有丝分裂剂类抗癌药耐药相关性显著。【结论】肿瘤细胞具有DNA修复能力 ,如核苷酸切割修复 ,更具体是具有ERCC2基因表达将表现为对主要是烷化剂和抗有丝分裂剂类抗癌药的耐药更多还原

【Abstract】 To investigate whether excision repair cross complementing rodent repair deficiency gene 2 (ERCC2)expression correlates with drug resistance in human tumor cell lines utilized by the anticancer drug screening program of the National Cancer Institute (NCI). With Western blot analysis, ERCC2 protein levels of 60 human tumor cell lines were determined and compared with the patterns of cytotoxicity (determined by sulforhodamine B assay) of 170 anticancer drugs. ERCC2 protein levels had a wide range of expression including undetectable levels in 6 cell lines. ERCC2 protein levels were found to be significantly correlated with resistance of the tumor cells to 28 out of 170 chemotherapeutic agents. Considering the mechanism of action, ERCC2 expression was significantlyrelated toresistance of thetumor cells toalkylatingagents or tubulin active antimitotic agents. [Conclusion] The present study suggests that ERCC2, and perhaps NER in general, is a contributing factor to alkylating agents and tubulin active antimitotic agents resistance in human tumor cell lines.更多还原