The possible involvement of chemical mediator(s) in the induction of the antitumor effects of recombinant human tumor necrosis factor-α (rTNF-α) on Meth A fibrosarcoma (Meth A) in mice was studied. On day 7 after intradermal implantation of Meth A in mice, rTNF-α caused tumor necrosis and inhibited the tumor growth. Ketanserin, cyproheptadine, and spiperone [serotonin (5-HT) receptor blockers] inhibited or attenuated the antitumor effects of rTNF-α, but the other types of receptor blockers tested (histamine H1 and H2, adrenaline α and β, dopamine, and acetylcholine receptor blockers) did not. The large i.v. doses of 5-HT caused tumor necrosis and inhibited tumor growth in mice when given i.v. on day 7 but not when given on day 3 after Meth A implantation, which effects closely resemble those of rTNF-α. Its antitumor effects were completely inhibited by the 5-HT receptor blockers. 5-HT, like rTNF-α, showed no cytotoxicity against in vitro cultured Meth A cells. The results suggest that 5-HT is, at least in part, important for the induction of antitumor effects of rTNF-α on Meth A in mice.

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©1988 American Association for Cancer Research.
1988
American Association for Cancer Research, Inc.