Chen Zhong-ping, Malapetsa Areti, Monks Anne, Myers Timothy G, Mohr Gérard, Sausville Edward A, Scudiero Dominic A, Panasci Lawrence C
Cancer Center, Sun Yat-sen University, Guangzhou 510060, P. R. China.
Ai Zheng. 2002 Mar;21(3):233-9.
BACKGROUND & OBJECTIVE: Nucleotide excision repair (NER) is a multi-enzyme DNA repair system in eukaryotes. Several NER genes in this system including XPA, XPB, ERCC1, and ERCC2 (XPD) have been implicated in anticancer drug resistance in human tumor cells. This study was designed to investigate the relationship between the expression of NER protein and the drug-resistance of human tumor cell lines.
In this study, The authors assessed the levels of the above mentioned proteins, by utilizing Western blot analysis, in the USA National Cancer Institute (NCI) panel of 60 human tumor cell lines and correlated to the cytotoxicity patterns of 170 compounds that constitute the standard agent (SA) database.
The ERCC1, XPB, and XPD protein expression patterns yielded significant negative Pearson correlations with 13, 17, and 32 out of the 170 compounds, respectively (P < 0.05). XPA produced a random assortment of negative and positive correlations and did not appear to confer an overall resistance or sensitivity to these drugs. Protein expression was also compared with a pre-defined categorisation of the standard agents into six mechanism-of-action (MOA) groups resulting in an inverse association between XPD and alkylating agent sensitivity.
Our present data demonstrate that XPD protein levels correlate with resistance to alkylating agents in human tumor cell lines, suggesting that XPD plays an important role in the development of this resistance.
核苷酸切除修复（NER）是真核生物中的一种多酶DNA修复系统。该系统中的几个NER基因，包括XPA、XPB、ERCC1和ERCC2（XPD），已被证实与人类肿瘤细胞的抗癌药物耐药性有关。本研究旨在探讨NER蛋白表达与人类肿瘤细胞系耐药性之间的关系。
在本研究中，作者利用蛋白质印迹分析评估了美国国立癌症研究所（NCI）的60种人类肿瘤细胞系中上述蛋白的水平，并将其与构成标准药物（SA）数据库的170种化合物的细胞毒性模式相关联。
ERCC1、XPB和XPD蛋白表达模式分别与170种化合物中的13种、17种和32种呈显著负Pearson相关性（P < 0.05）。XPA产生了正负相关性的随机组合，似乎并未赋予对这些药物的总体耐药性或敏感性。还将蛋白表达与标准药物预先定义的六种作用机制（MOA）组分类进行了比较，结果显示XPD与烷化剂敏感性呈负相关。
我们目前的数据表明，XPD蛋白水平与人类肿瘤细胞系对烷化剂的耐药性相关，这表明XPD在这种耐药性的发展中起重要作用。
