Effect of topoisomerase modulators on cisplatin cytotoxicity in human ovarian carcinoma cells.
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.
Katz
E J
EJ
Department of Medicine, University of California, San Diego, La Jolla 92093.
Vick
J S
JS
Kling
K M
KM
Andrews
P A
PA
Howell
S B
SB
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D002166:Camptothecin / Q000494:pharmacology; D002460:Cell Line; D002945:Cisplatin / Q000627:therapeutic use*; D004264:DNA Topoisomerases, Type I / Q000187:drug effects*; D004347:Drug Interactions; D005047:Etoposide / Q000494:pharmacology*; D005260:Female; D006801:Humans; D009285:Naphthoquinones / Q000494:pharmacology; D009675:Novobiocin / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology
D000903:Antibiotics, Antineoplastic; D009285:Naphthoquinones; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D009675:Novobiocin; C014638:beta-lapachone; D005047:Etoposide; D004264:DNA Topoisomerases, Type I; D002945:Cisplatin; D002166:Camptothecin