Newman E M, Lu Y, Kashani-Sabet M, Kesavan V, Scanlon K J
Division of Pediatrics, City of Hope National Medical Center, Duarte, CA 91010.
Biochem Pharmacol. 1988 Feb 1;37(3):443-7. doi: 10.1016/0006-2952(88)90212-2.
Some properties of the human ovarian carcinoma line A2780 and a subline three times more resistant than the parent line to cisplatin are compared in this report. The rates of uptake and release of cisplatin were similar in the two cell lines. Resistance to cisplatin was associated with: (a) cross-resistance to 5-fluorouracil and methotrexate; (b) a 2.5-fold increase in thymidylate synthase, as measured by both enzyme activity and the capacity to complex 5-fluorodeoxyuridylate; and (c) an increase in the intracellular pools of 5,10-methylenetetrahydrofolate and tetrahydrofolate. These data suggest that cross-resistance to 5-fluorouracil and methotrexate in A2780 cells may be a consequence of increases in their respective target enzymes.
本报告比较了人卵巢癌细胞系A2780及其对顺铂耐药性比亲代细胞系高三倍的亚系的一些特性。顺铂在这两种细胞系中的摄取和释放速率相似。对顺铂的耐药性与以下因素有关：(a) 对5-氟尿嘧啶和甲氨蝶呤的交叉耐药性；(b) 通过酶活性和与5-氟脱氧尿苷酸结合的能力测定，胸苷酸合成酶增加2.5倍；(c) 5,10-亚甲基四氢叶酸和四氢叶酸的细胞内池增加。这些数据表明，A2780细胞对5-氟尿嘧啶和甲氨蝶呤的交叉耐药性可能是其各自靶酶增加的结果。
