[Studies on reversing effect of multidrug resistance by dipyridamole. I. modulation of epirubicin-induced effects on cell proliferation and cell cycle by dipyridamole].

Dipyridamole, a nucleoside membrane transport inhibitor, enhanced the cytotoxicity of epirubicin for mouse leukemia P388 cells by a factor of 1.8-fold and that for 30-fold doxorubicin-resistant sublines of P388 cells (P388/DOX) by a factor of 6.5-fold. This interaction was shown to be truly synergistic by DNA histogram and median effect analysis. The dipyridamole enhancement of the cytotoxicity of epirubioin was a dose-dependent effect; it was greatest when cells were exposed to dipyridamole before treatment with epirubicin. In cell cycle experiments, 1-5 microM dipyridamole increased the accumulation of G2 + M phase produced by the treatment with 0.5-1 microM epirubicin. Dipyridamole, however, did not appear to alter the patterns of DNA histogram in sensitive cells. These results suggest that the increase of the accumulation of G2 + M phase in resistant cells is an important factor for the interaction between epirubicin and dipyridamole.