Scanlon K J, Kashani-Sabet M, Sowers L C
Department of Medical Oncology, City of Hope National Medical Center, Duarte, CA 91010.
Cancer Commun. 1989;1(4):269-75.
Biochemical differences were demonstrated between two cell lines derived from a human colon carcinoma (HCT8), one sensitive (HCT8S), and one 4.3-fold resistant to cisplatin (HCT8DDP). The cisplatin-resistant cell line overexpressed five enzymes (dihydrofolate reductase, thymidine 5'-monophosphate synthase, thymidine kinase, and DNA polymerase alpha and beta) believed to be important for DNA replicative and repair synthesis. In addition, the c-fos and c-H-ras oncogenes were also overexpressed in the HCT8DDP cells. This apparent overexpression was not associated with increases in gene copy number, it was related, however, to increased mRNA content. Expression of these key enzymes may be a significant factor in the development of clinical resistance to cisplatin. Further, these specific changes in cellular metabolism associated with cisplatin resistance may be exploited by the use of nucleoside analogues.
在源自人结肠癌（HCT8）的两种细胞系之间发现了生化差异，一种对顺铂敏感（HCT8S），另一种对顺铂具有4.3倍抗性（HCT8DDP）。顺铂抗性细胞系过表达了五种酶（二氢叶酸还原酶、胸苷5'-单磷酸合酶、胸苷激酶以及DNA聚合酶α和β），这些酶被认为对DNA复制和修复合成很重要。此外，c-fos和c-H-ras癌基因在HCT8DDP细胞中也过表达。这种明显的过表达与基因拷贝数的增加无关，然而，它与mRNA含量的增加有关。这些关键酶的表达可能是临床对顺铂产生抗性的一个重要因素。此外，使用核苷类似物可能会利用这些与顺铂抗性相关的细胞代谢的特定变化。
