Potentiation of antimetabolite antitumor activity in vivo by dipyridamole and amphotericin B.
Previous studies have shown that dipyridamole (DP), a potent nucleoside transport inhibitor blocking the rescue effect of exogenous nucleosides, markedly potentiates the cytotoxicity of antimetabolites. However, no enhancement of the chemotherapeutic effect of antimetabolites by DP in vivo has yet been reported. This study provided evidence that the combination of DP and amphotericin B (AmB) significantly potentiated the inhibitory effect of 5-fluorouracil (FU) or methotrexate (MTX) against a panel of transplantable tumors including sarcoma 180, cervical carcinoma U14, and Lewis lung carcinoma in mice. No significant increase in toxicity was induced by this combination in treated mice. Our results indicate that the combination of DP and AmB with antimetabolites is potentially useful in cancer chemotherapy.
Cao
S S
SS
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing.
Zhen
Y S
YS
D000666:Amphotericin B / Q000627:therapeutic use* / Q000633:toxicity; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use* / Q000633:toxicity; D004176:Dipyridamole / Q000627:therapeutic use* / Q000633:toxicity; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use / Q000633:toxicity; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D012510:Sarcoma 180 / Q000188:drug therapy; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy
D000964:Antimetabolites, Antineoplastic; D004176:Dipyridamole; D000666:Amphotericin B; D005472:Fluorouracil; D008727:Methotrexate