Interaction between methotrexate and indomethacin on a human normal haemopoietic cell line

Abstract

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. Indomethacin (1 μg ml−1) increased the reduction of lymphoblast growth caused by methotrexate (10–80 ng ml−1). Indomethacin (0.1 and 1 μg ml−1) potentiated the cytotoxicity of methotrexate (20 and 40 ng ml−1) after 4 days in culture. Indomethacin (0.4 μg 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. 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. 1995 British Pharmacological Society