Study of 5HT3 and HT4 receptor expression in HT29 cell line and human colon adenocarcinoma tissues.
BACKGROUND
Serotonin (5HT) has been shown to be a mitogenic factor in several carcinomas. Its mitogenic effect is elicited through a wide range of 5HT receptor subtypes. In this study, the effects of 5HT, 5HT3 (1-phenylbiguanide hydrochloride) and 5HT4 (cisapride) agonists in promoting the growth of the HT29 cell line and the growth-inhibition effect of the 5HT3 receptor antagonist (Y-25130 hydrochloride) and 5HT4 receptor antagonist (RS 23597-190) were investigated. The expressions of 5HT3 and 5HT4 receptors in human colon cancer tissues and the HT29 cell line were studied.


METHODS
The growth-promoting and growth-inhibition effects of 5-HT, 5HT3 and 5HT4 agonists and antagonists on the HT29 cell line were studied using MTT assay. Receptor expression has been demonstrated by western blotting.


RESULTS
The results showed that 5HT, 5HT3, and 5HT4 agonists caused significant proliferation of HT29 cells. 5HT3 and 5HT4 receptor antagonists had an inhibitory effect on the growth of these cells. Western blot analysis gave bands from colon tissue extracts and the HT29 cell line.


CONCLUSIONS
The results indicate which 5HT3 and 5HT4 receptors are significantly expressed in both colon cancer tissue and the HT29 cell line. Expression for the 5HT3 receptor is more potent. Furthermore, 5HT plays a mitogenic role in colon cancer cells and antagonists of 5HT3, and 5HT4 receptors can inhibit cancer cell growth.
Ataee
Ramin
R
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Ajdary
Soheila
S
Rezayat
Mehdi
M
Shokrgozar
Mohammad Ali
MA
Shahriari
Shadab
S
Zarrindast
Mohammad Reza
MR
D000230:Adenocarcinoma / Q000378:metabolism*; D062365:Aminobenzoates / Q000494:pharmacology; D001645:Biguanides / Q000494:pharmacology; D015153:Blotting, Western; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D020117:Cisapride / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000378:metabolism*; D019073:HT29 Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D010078:Oxazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism*; D044422:Receptors, Serotonin, 5-HT4 / Q000378:metabolism*; D058827:Serotonin 5-HT3 Receptor Agonists / Q000494:pharmacology; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000494:pharmacology; D058828:Serotonin 5-HT4 Receptor Agonists / Q000494:pharmacology; D058832:Serotonin 5-HT4 Receptor Antagonists / Q000494:pharmacology; D062366:para-Aminobenzoates
C084177:3-(piperidine-1-yl)propyl 4-amino-5-chloro-2-methoxybenzoate hydrochloride; D062365:Aminobenzoates; D001645:Biguanides; D019086:Bridged Bicyclo Compounds, Heterocyclic; D010078:Oxazines; D010880:Piperidines; D044406:Receptors, Serotonin, 5-HT3; D058827:Serotonin 5-HT3 Receptor Agonists; D058831:Serotonin 5-HT3 Receptor Antagonists; D058828:Serotonin 5-HT4 Receptor Agonists; D058832:Serotonin 5-HT4 Receptor Antagonists; D062366:para-Aminobenzoates; D044422:Receptors, Serotonin, 5-HT4; C070671:azasetron; D020117:Cisapride; C008846:phenyl biguanide