amphotericin-b and Sarcoma-180

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.

Topics: Amphotericin B; Animals; Antineoplastic Agents; Biological Transport; Dipyridamole; Drug Synergism; Female; Leukemia L1210; Male; Methotrexate; Mice; Nucleosides; Sarcoma 180; Tumor Cells, Cultured

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.

Topics: Amphotericin B; Animals; Antimetabolites, Antineoplastic; Dipyridamole; Drug Evaluation, Preclinical; Drug Synergism; Drug Therapy, Combination; Female; Fluorouracil; Lung Neoplasms; Male; Methotrexate; Mice; Mice, Inbred C57BL; Neoplasm Transplantation; Sarcoma 180; Uterine Cervical Neoplasms

Topics: Alkylating Agents; Amphotericin B; Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Cyclophosphamide; Drug Evaluation, Preclinical; Drug Synergism; Drug Therapy, Combination; Leukemia L1210; Lymphoma, Non-Hodgkin; Mice; Neoplasm Transplantation; Neoplasms, Experimental; Rats; Sarcoma 180; Thiotepa

Topics: Amphotericin B; Animals; Carbon Isotopes; Cell Membrane Permeability; Culture Media; Culture Techniques; DNA; Histones; Humans; Leucine; Potassium; Potassium Isotopes; Protein Biosynthesis; RNA; Sarcoma 180; Thymidine; Uridine