Combined effects of methotrexate and 5-fluoropyrimidine on human breast cancer cells in serum-free culture

Ross C. Donehower, Joseph C. Allegra, Marc E. Lippman, Bruce A. Chabner

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

The combined effects of methotrexate and 5-fluoropyrimidines on the growth of a human breast cancer cell line in serum-free hormone-supplemented medium, lacking nucleosides, have been studied. All combinations of methotrexate (10-50 nM) and 5-fluorodeoxyuridine (10-100 nM) resulted in at least additive inhibition of cell growth and when analyzed by 50% response isobologram demonstrated synergism. Combinations of methotrexate (10-50 nM) and 5-fluorouracil (0.04-0.4 μM) gave enhanced inhibition as compared to single agents, but 50% response isobologram revealed only additive effects. The combination was most effective when methotrexate was added to the cultures prior to the 5-fluoropyrimidines or when the drugs were added simultaneously. The addition of 5-fluoropyrimidine prior to methotrexate appears to decrease the effect of the antifol on purine synthesis and lessen the cytotoxicity of the combination in this cell line.

Original languageEnglish (US)
Pages (from-to)655-661
Number of pages7
JournalEuropean Journal of Cancer (1965)
Volume16
Issue number5
DOIs
StatePublished - May 1980

ASJC Scopus subject areas

  • Medicine(all)

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