Lu Y, Han J, Scanlon K J
Department of Medical Oncology, City of Hope National Medical Center, Duarte, California 91010.
J Biol Chem. 1988 Apr 5;263(10):4891-4.
In this study, A2780 human ovarian carcinoma cells were grown in folinic acid in contrast to folic acid, and the molecular and biochemical properties of cisplatin-resistant A2780 cells were analyzed for changes in the dTMP synthase cycle. At concentrations of folinic acid that were optimal for cell growth (10(-8) M), the ED50 for cisplatin was 2.5 and 43 microM in the A2780S and A2780DDP cells, respectively. Resistance to cisplatin was associated with a 2-fold cross-resistance to 5-fluorodeoxyuridine and 5-fluorouracil as well as a 3-fold increase in both dTMP synthase activity and mRNA. The ED50 for methotrexate was similar in both A2780S and A2780DDP cells (1.2 microM). When both the A2780S and A2780DDP cells were grown in folinic acid, there was no significant difference in the level of dihydrofolate reductase activity. This data would suggest that cisplatin resistance is associated with changes in folate metabolism.
在本研究中，将A2780人卵巢癌细胞置于亚叶酸而非叶酸中培养，并分析顺铂耐药A2780细胞的分子和生化特性，以观察其在dTMP合酶循环中的变化。在对细胞生长最适宜的亚叶酸浓度（10^(-8) M）下，A2780S和A2780DDP细胞中顺铂的半数有效剂量（ED50）分别为2.5和43微摩尔。对顺铂的耐药性与对5-氟脱氧尿苷和5-氟尿嘧啶的2倍交叉耐药相关，同时dTMP合酶活性和mRNA均增加了3倍。甲氨蝶呤在A2780S和A2780DDP细胞中的ED50相似（1.2微摩尔）。当A2780S和A2780DDP细胞均在亚叶酸中培养时，二氢叶酸还原酶活性水平无显著差异。这些数据表明顺铂耐药性与叶酸代谢变化有关。
