Effect of bestatin on syngeneic tumors in mice

The antitumor effect of bestatin against syngeneic tumors such as colon adenocarcinoma 26 (colon 26) and myeloid leukemia C1498 ( C1498 ) was investigated. Bestatin effectively inhibited the growth of both tumors in vivo. The inhibition observed for colon 26 was the largest when bestatin was administered on days 1 to 5 after transplantation of the tumor. The inhibition of C1498 was the largest when bestatin was administered on days 7 to 11. In contrast to these results, bestatin was not at all inhibitory to either tumor line in vitro. Thus, the effect of bestatin administration on the functions of the spleen cells of mice bearing tumors was examined. Spleen cells taken from mice bearing colon 26 and C1498 did not neutralize the corresponding tumor. However, when bestatin was administered to these mice, spleen cells from the administered mice did neutralize the corresponding tumor. Bestatin enhanced antibody-dependent cell-mediated cytotoxicity and natural killer cell activity of the spleen cells of colon 26-bearing mice. Further, bestatin did not inhibit the growth of colon 26 in BALB/c nu/nu mice. It was concluded that bestatin exhibits its antitumor effect against colon 26 and C1498 indirectly by immunomodulation via spleen cells and possibly via T cells.