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

✍ Scribed by Chun-Ming Tsai; Adi F. Gazdar; Reury-Perng Perng; Barnett S. Kramer

Publisher
John Wiley and Sons
Year
1991
Tongue
French
Weight
702 KB
Volume
47
Category
Article
ISSN
0020-7136

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✦ Synopsis

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 5fluorouracil (FUra) in 4 schedules on 2 human non-small-cell lung cancer cell lines (adenocarcinoma, NCLH23; bronchioalveolar-cell carcinoma, NCI-H358), and I 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 xhedule-dependent. This provides a rational basis for testing sequential MTX-FUra with a longer administration interval than usually employed clinically.

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