Biochemical and molecular properties of cisplatin-resistant A2780 cells grown in folinic acid.
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.
Lu
Y
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Department of Medical Oncology, City of Hope National Medical Center, Duarte, California 91010.
Han
J
J
Scanlon
K J
KJ
D002460:Cell Line; D002945:Cisplatin / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000235:genetics; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007700:Kinetics; D002955:Leucovorin / Q000494:pharmacology*; D010051:Ovarian Neoplasms; D012334:RNA, Neoplasm / Q000235:genetics; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics; D013940:Thymidylate Synthase / Q000235:genetics; D014158:Transcription, Genetic
D004273:DNA, Neoplasm; D012334:RNA, Neoplasm; D013762:Tetrahydrofolate Dehydrogenase; D013940:Thymidylate Synthase; D002945:Cisplatin; D002955:Leucovorin