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 b...

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Bibliographic Details
Published in:Cancer chemotherapy and pharmacology 1989-09, Vol.24 (3), p.181-186
Main Authors: Cao, S S, Zhen, Y S
Format: Article
Language:English
Subjects:
Amphotericin B - therapeutic use
Amphotericin B - toxicity
Animals
Antimetabolites, Antineoplastic - therapeutic use
Antimetabolites, Antineoplastic - toxicity
Antineoplastic agents
Biological and medical sciences
Chemotherapy
Dipyridamole - therapeutic use
Dipyridamole - toxicity
Drug Evaluation, Preclinical
Drug Synergism
Drug Therapy, Combination
Female
Fluorouracil - therapeutic use
Fluorouracil - toxicity
Lung Neoplasms - drug therapy
Male
Medical sciences
Methotrexate - therapeutic use
Methotrexate - toxicity
Mice
Mice, Inbred C57BL
Neoplasm Transplantation
Pharmacology. Drug treatments
Sarcoma 180 - drug therapy
Uterine Cervical Neoplasms - drug therapy
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Summary: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.
ISSN:0344-5704
1432-0843
DOI:10.1007/bf00300240