Important role of serotonin in the antitumor effects of recombinant human tumor necrosis factor-alpha in mice.
The possible involvement of chemical mediator(s) in the induction of the antitumor effects of recombinant human tumor necrosis factor-alpha (rTNF-alpha) on Meth A fibrosarcoma (Meth A) in mice was studied. On day 7 after intradermal implantation of Meth A in mice, rTNF-alpha 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-alpha, but the other types of receptor blockers tested (histamine H1 and H2, adrenaline alpha and beta, 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-alpha. Its anti-tumor effects were completely inhibited by the 5-HT receptor blockers. 5-HT, like rTNF-alpha, 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-alpha on Meth A in mice.
Manda
T
T
Department of Pharmacology, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Nishigaki
F
F
Mori
J
J
Shimomura
K
K
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003533:Cyproheptadine / Q000494:pharmacology; D005260:Female; D005354:Fibrosarcoma / Q000473:pathology; D007650:Ketanserin / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013134:Spiperone / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D011985:Receptors, Serotonin; D011994:Recombinant Proteins; D012702:Serotonin Antagonists; D014409:Tumor Necrosis Factor-alpha; D003533:Cyproheptadine; D012701:Serotonin; D013134:Spiperone; D007650:Ketanserin