[Potentiated antitumor effect of methotrexate by dipyridamole]

Previous studies have shown that the cytotoxicity of antimetabolites to mammalian cells can be reversed by exogenous nucleosides. Dipyridamole (DP), a nucleoside transport inhibitor, can block the reversal effect, thus potentiating the cytotoxicity of antimetabolites to tumor cells. However, potentiation of antimetabolites by DP in vivo has not yet been reported. In this study we found that thymidine and hypoxanthine markedly reversed the cytotoxicity of methotrexate (MTX) to murine leukemia L1210 cells, and DP effectively blocked the reversal in vitro. In combination with amphotericin B (AmB), DP enhanced the inhibitory effect of MTX on sarcoma 180 in mice without a significant increase in toxicity. To our knowledge this is the first report that the combination of DP and AmB potentiates the antitumor effect of an antimetabolite in vivo. Results suggest that this combination may be potentially useful in cancer chemotherapy.