Interaction between methotrexate and indomethacin on a human normal haemopoietic cell line.
1. The interaction between methotrexate and indomethacin has been examined, at a physiological folate concentration (20 nM), on a human normal lymphoblast-like cell line (RPMI 1788) in vitro. 2. Indomethacin (1 microgram ml-1) increased the reduction of lymphoblast growth caused by methotrexate (10-80 ng ml-1). 3. Indomethacin (0.1 and 1 microgram ml-1) potentiated the cytotoxicity of methotrexate (20 and 40 ng ml-1) after 4 days in culture. 4. Indomethacin (0.4 micrograms ml-1) reduced the accumulation of tritium in lymphoblasts incubated with [3H]-methotrexate after 30 min; therefore initial drug accumulation was not responsible for the potentiation seen after 4 days. 5. If indomethacin increases the killing of human cancer cells by methotrexate in vivo, with a smaller potentiation on lymphoblasts, this combination may be beneficial in treating human malignancy.
Hollingsworth
S J
SJ
Department of Surgery, King's College School of Medicine and Dentistry, Rayne Institute, London.
Shankley
N P
NP
Anderson
E M
EM
Bennett
A
A
D000328:Adult; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004357:Drug Synergism; D005492:Folic Acid / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007213:Indomethacin / Q000378:metabolism / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008727:Methotrexate / Q000378:metabolism / Q000494:pharmacology*; D014316:Tritium / Q000378:metabolism; D044465:White People
D014316:Tritium; D005492:Folic Acid; D007213:Indomethacin; D008727:Methotrexate