论文部分内容阅读
背景与目的:核苷酸切除修复(Nucleotideexcisionrepair,NER)是真核细胞中的DNA修复多酶系统,它可能与人肿瘤细胞对抗癌药的耐药有关。本实验将探讨NER蛋白(XPA,XPB,XPD和ERCC1)的表达与人肿瘤细胞耐药的关系。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60株人肿瘤细胞的ERCC1,XPA,XPBXPD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:ERCC1,XPB和XPD的蛋白表达与抗癌药物敏感性呈负相关,在170种抗癌药物中分别有13,17和32种的耐药性与上述蛋白水平相关性显著或非常显著(P<0.05)。而XPA的表达与药物敏感性无明显正/负相关。根据已确定的6种药物作用机理分析,肿瘤细胞XPD表达与其对烷化剂类抗癌药耐药相关性显著。结论:本实验结果肿瘤细胞的XPD蛋白表达与烷化剂类抗癌药的耐药相关,提示XPD在肿瘤细胞耐药过程中起重要作用。
BACKGROUND & OBJECTIVE: Nucleotide excision repair (NER) is a DNA repair multi-enzyme system in eukaryotic cells. It may be related to the resistance of human tumor cells to anticancer drugs. This experiment will explore the relationship between the expression of NER protein (XPA, XPB, XPD and ERCC1) and human tumor cell resistance. Methods: Western blot was used to detect the expression of ERCC1, XPA and XPBXPD in 60 human tumor cells screened by the National Cancer Institute (NCI) for anti-cancer drugs. The results were correlated with the cytotoxicity of 170 anticancer drugs analysis. Results: The protein expressions of ERCC1, XPB and XPD were negatively correlated with the sensitivity of anti-cancer drugs. Among the 170 anti-cancer drugs, 13, 17 and 32 were significantly or significantly related to the above protein levels P <0.05). The expression of XPA had no significant positive or negative correlation with drug sensitivity. According to the identified mechanisms of action of six drugs, the expression of XPD in tumor cells is significantly correlated with drug resistance to alkylating agents. Conclusion: Our results showed that the expression of XPD in tumor cells was related to the resistance of alkylating agents, suggesting that XPD plays an important role in the drug resistance of tumor cells.