Li Q, Ding L, Yu J J, Mu C, Tsang B, Bostick-Bruton F, Reed E
Medical Ovarian Cancer Section, Developmental Therapeutics Department, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD 20892, USA.
Int J Oncol. 1998 Nov;13(5):987-92. doi: 10.3892/ijo.13.5.987.
Nucleotide excision repair (NER) is the DNA repair pathway by which cisplatin-induced damage is removed from DNA in human cells. ERCC-1 is one of the essential proteins in NER, and is essential for life. Enhanced ERCC-1 expression has been associated with clinical and cellular resistance to cisplatin. We therefore carried out this study to investigate the effect of cisplatin on ERCC-1 protein expression in A2780/CP70 human ovarian cancer cells. Western blot analysis showed that ERCC-1 protein levels were increased to more than 3 times control after a 1 h cisplatin exposure to A2780/CP70 cells in culture. This increase was time- and concentration-dependent. The effect of cisplatin was maximal at 40 mM and peaked 24-48 h after exposure to the drug. These results extend our previous observations that ERCC-1 mRNA expression is induced by cisplatin in this system. TPA, a known AP-1 activator and tumor-promoting phorbol ester, also induced ERCC-1 protein to the same extent as cisplatin, but did not synergize with cisplatin in this regard. These findings suggest that ERCC-1 gene up-regulation in these cells can result through a DNA damage-response pathway, or through the induction of AP-1 activity, independent of the occurrence of DNA damage.
核苷酸切除修复（NER）是一种DNA修复途径，通过该途径可将顺铂诱导的损伤从人类细胞的DNA中去除。ERCC-1是NER中的一种关键蛋白，对生命至关重要。ERCC-1表达增强与顺铂的临床及细胞耐药性相关。因此，我们开展了本研究，以探讨顺铂对A2780/CP70人卵巢癌细胞中ERCC-1蛋白表达的影响。蛋白质印迹分析表明，在培养的A2780/CP70细胞中，顺铂作用1小时后，ERCC-1蛋白水平增加至对照的3倍以上。这种增加具有时间和浓度依赖性。顺铂的作用在40 mM时最大，在接触药物后24 - 48小时达到峰值。这些结果扩展了我们之前的观察结果，即在该系统中顺铂可诱导ERCC-1 mRNA表达。TPA是一种已知的AP-1激活剂和促肿瘤佛波酯，它诱导ERCC-1蛋白的程度与顺铂相同，但在这方面与顺铂没有协同作用。这些发现表明，这些细胞中ERCC-1基因的上调可通过DNA损伤反应途径或通过AP-1活性的诱导产生，与DNA损伤的发生无关。
