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...

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Bibliographic Details
Published in:The Journal of biological chemistry 1988-04, Vol.263 (10), p.4891-4894
Main Authors: Lu, Y, Han, J, Scanlon, K J
Format: Article
Language:English
Subjects:
Biological and medical sciences
Cell Line
Cell metabolism, cell oxidation
Cell physiology
Cisplatin - pharmacology
DNA, Neoplasm - genetics
Drug Resistance
Female
Fundamental and applied biological sciences. Psychology
Humans
Kinetics
Leucovorin - pharmacology
Molecular and cellular biology
Ovarian Neoplasms
RNA, Neoplasm - genetics
Tetrahydrofolate Dehydrogenase - genetics
Thymidylate Synthase - genetics
Transcription, Genetic
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Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1016/S0021-9258(18)68869-6