[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.
Hayashi
A
A
Department of Pharmacology and Toxicology, Tohoku College of Pharmacy, Sendai, Japan.
Furusawa
S
S
Takayanagi
M
M
Takayanagi
Y
Y
Sasaki
K
K
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004176:Dipyridamole / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple; D004357:Drug Synergism; D015251:Epirubicin / Q000494:pharmacology*; D007941:Leukemia P388 / Q000473:pathology*; D051379:Mice; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D010975:Platelet Aggregation Inhibitors; D015251:Epirubicin; D004176:Dipyridamole