Schedule-dependent in vitro combination effects of methotrexate and 5-fluorouracil in human tumor cell lines

C. M. Tsai, A. F. Gazdar, R. P. Perng, B. S. Kramer

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Because of conflicting reports of clinical synergy, we used the tetrazolium-based colorimetric (MTT) assay to test in vitro combination effects of methotrexate (MTX) plus 5-fluorouracil (FUra) in 4 schedules on 2 human non-small-cell lung cancer cell lines (adenocarcinoma, NCI-H23; bronchioalveolar-cell carcinoma, NCI-H358), and 1 human colorectal adenocarcinoma cell line (SNU-CI). The complete 3 dimensional set of isoboles in the dose range under study was generated by a microcomputer-based method. We found that the combination effects of 8-hr sequential FUra-MTX, simultaneous administration of MTX-FUra, and 8-hr sequential MTX-FUra were clearly antagonistic for all 3 cell lines. In contrast, the combination cytotoxic effects of 24-hr sequential MTX-FUra were much more active. Our in vitro model thus clearly shows that MTX-FUra interactions are highly schedule-dependent. This provides a rational basis for testing sequential MTX-FUra with a longer administration interval than usually employed clinically.

Original languageEnglish (US)
Pages (from-to)401-407
Number of pages7
JournalInternational Journal of Cancer
Volume47
Issue number3
StatePublished - 1991

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Tumor Cell Line
Methotrexate
Fluorouracil
Appointments and Schedules
Cell Line
Adenocarcinoma
Microcomputers
In Vitro Techniques
Non-Small Cell Lung Carcinoma
Carcinoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Schedule-dependent in vitro combination effects of methotrexate and 5-fluorouracil in human tumor cell lines. / Tsai, C. M.; Gazdar, A. F.; Perng, R. P.; Kramer, B. S.

In: International Journal of Cancer, Vol. 47, No. 3, 1991, p. 401-407.

Research output: Contribution to journalArticle

Tsai, C. M. ; Gazdar, A. F. ; Perng, R. P. ; Kramer, B. S. / Schedule-dependent in vitro combination effects of methotrexate and 5-fluorouracil in human tumor cell lines. In: International Journal of Cancer. 1991 ; Vol. 47, No. 3. pp. 401-407.
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