The combined effects of adriamycin (ADM) and dipyridamole (DP) on lung metastasis of B16 melanoma cells in mice were investigated. First, the antitumor effects of ADM and DP were examined both in vitro and in vivo. The clonogenicity of B16 melanoma cells was suppressed by the combination of ADM and the nontoxic dose of DP in vitro, and growth of the B16 melanoma solid tumor implanted subcutaneously in mice was inhibited with this drug combination, compared to findings with ADM alone in vivo. To examine events related to experimental lung metastasis, 2 X 105 B16 melanoma cells were given intravenously into the tail vein of mice and the efficacy was determined by counting the number of metastatic tumor nodules. DP in doses of 25-100 mg/kg given alone reduced the number of metastasis to about 85% that in the control group. ADM in doses of 1-4 mg/kg for 3 days inhibited the metastasis, in a dose-dependent manner. When combined with DP, the antimetastatic effect of ADM was enhanced and the number of metastasis prominently decreased, compared to single application of the drug (p < 0.05). We speculate that ADM given concomitantly with DP may have the potential to inhibit metastatic growth of a tumor.
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