Depletion of serotonin and selective inhibition of 2B receptor suppressed tumor angiogenesis by inhibiting endothelial nitric oxide synthase and extracellular signal-regulated kinase 1/2 phosphorylation.

ABSTRACT: The effects of serotonin (5-HT) on tumor growth are inconsistent. We investigated whether a decreased level of 5-HT affected tumor growth using 5-HT transporter knockout (5-HTT(-/-)) mice, which showed 5-HT depletion. When cancer cells were injected subcutaneously into both 5-HTT(-/-) and 5-HTT(+/+) mice, the tumor growth was markedly attenuated in 5-HTT(-/-) mice. Serotonin levels in the blood, forebrain, and tumors of 5-HTT(-/-) mice bearing tumors were significantly smaller than those of their 5-HTT(+/+) littermates. However, 5-HT did not increase cancer cells' proliferation in vitro. When we applied 5-HTT inhibitors to the wild mice bearing tumors, they did not inhibit tumor growth. The endothelial nitric oxide synthase (eNOS) expressions in tumors were reduced in 5-HTT(-/-) mice compa

SUBMITTER: Asada M 

PROVIDER: S-EPMC2657884 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature