Serotonin (5-hydroxytryptamine, 5-HT) is known to be a mitogenic factor in several malignancies. It elicits its mitogenic effect through a wide range of 5-HT receptor subtypes and several internal cellular transcription pathways. According to wide distribution of 5-HT3 and 5-HT4 receptors in the gastrointestinal tract, the main aim of this study was to investigate the effect of these receptor agonists and antagonists in a colorectal cell line. In cell culture, we investigated the effects of 5-HT, 5-HT3 and 5-HT4 receptor agonists and antagonists on proliferation of HT29 cells. We also tested apoptosis for the receptor antagonists with TUNEL apoptosis test. In addition, we assayed effects of 5-HT receptor antagonists on cell cycle kinetics with flow cytometery. Proliferation assay revealed that phenylbiguanide (a 5-HT3 receptor selective agonist) increased proliferation of HT29 cells significantly and Y25130 hydrochloride (a 5-HT3 receptor antagonist) had the opposite effect; but for 5-HT4 receptor antagonist, these effects were not significant. In addition, potent apoptotic and cell cycle arresting effect was found for a selective 5-HT3 receptor antagonist but we have not seen any significant effect for the 5-HT4 receptor antagonist. The findings of this study provide strong evidence for the potential role of 5-HT3 receptors in colorectal cancer.
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