Katz E J, Vick J S, Kling K M, Andrews P A, Howell S B
Department of Medicine, University of California, San Diego, La Jolla 92093.
Eur J Cancer. 1990;26(6):724-7. doi: 10.1016/0277-5379(90)90127-f.
The in vitro interaction of modulators of topoisomerase I and II with cisplatin in human ovarian carcinoma cells might be synergistic. The interactions were evaluated by median effect analysis of survival data derived from continuous exposure to drug combinations for 10 days in colony-forming assays. The interaction between cisplatin and the topoisomerase I inhibitor camptothecin and the topoisomerase I activator beta-lapachone was additive, as was that between cisplatin and the topoisomerase II inhibitor novobiocin. Despite the clinical efficacy of the combination of etoposide (a topoisomerase II inhibitor) and cisplatin, the combination index at 50% cell kill indicated antagonism between these two drugs. Thus, biochemical synergism at the cellular level is not a prerequisite of improved therapeutic efficacy.
拓扑异构酶I和II调节剂与人卵巢癌细胞中顺铂的体外相互作用可能具有协同性。通过在集落形成试验中对连续10天暴露于药物组合的生存数据进行中位效应分析来评估这种相互作用。顺铂与拓扑异构酶I抑制剂喜树碱以及拓扑异构酶I激活剂β-拉帕醌之间的相互作用是相加的，顺铂与拓扑异构酶II抑制剂新生霉素之间的相互作用也是如此。尽管依托泊苷（一种拓扑异构酶II抑制剂）与顺铂联合使用具有临床疗效，但50%细胞杀伤时的联合指数表明这两种药物之间存在拮抗作用。因此，细胞水平的生化协同作用并非提高治疗效果的先决条件。
