Tropisetron suppresses colitis-associated cancer in a mouse model in the remission stage

Amini-Khoei, Hossein. and Momeny, Majid. and Abdollahi, Alireza. and Dehpour, Ahmad Reza. and Amiri, Shayan. and Haj-Mirzaian, Arya. and Tavangar, Seyed Mohammad. and Ghaffari, Seyed Hamid. and Rahimian, Reza. and Ejtemaei Mehr, Shahram. (2016) Tropisetron suppresses colitis-associated cancer in a mouse model in the remission stage. International immunopharmacology, 36.

[img] Text
3.pdf

Download (1MB)

Abstract

Patients with inflammatory bowel disease (IBD) have a high risk for development of colitis-associated cancer (CAC). Serotonin is a neurotransmitter produced by enterochromaffin cells of the intestine. Serotonin and its receptors, mainly 5-HT3 receptor, are overexpressed in IBD and promote development of CAC through production of inflammatory cytokines. In the present study, we demonstrated the in vivo activity of tropisetron, a 5-HT3 receptor antagonist, against experimental CAC. CAC was induced by azoxymethane (AOM)/dextran sodium sulfate (DDS) in BALB/c mice. The histopathology of colon tissue was performed. Beta-catenin and Cox-2 expression was evaluated by immunohistochemistry as well as quantitative reverse transcription-PCR (qRT-PCR). Alterations in the expression of 5-HT3 receptor and inflammatory-associated genes such as Il-1β, Tnf-α, Tlr4 and Myd88 were determined by qRT-PCR. Our results showed that tumor development in tropisetron-treated CAC group was significantly lower than the controls. The qRT-PCR analysis demonstrated that the expression of 5-HT3 receptor was significantly increased following CAC induction. In addition, tropisetron reduced expression of β-catenin and Cox-2 in the CAC experimental group. The levels of Il-1β, Tnf-α, Tlr4 and Myd88 were significantly decreased upon tropisetron treatment in the AOM/DSS group. Taken together, our data show that tropisetron inhibits development of CAC probably by attenuation of inflammatory reactions in the colitis.

Item Type: Article
Uncontrolled Keywords: CAC,Serotonin,5-HT3 receptor,Colitis
Subjects: WI Digestive System
QU Biochemistry
QV pharmacology
Divisions: Reserach Vice-Chancellar Department > Cellular and Molecular Research Center
Depositing User: zahra bagheri .
Date Deposited: 31 Dec 2017 05:17
Last Modified: 18 Feb 2018 09:35
URI: http://eprints.skums.ac.ir/id/eprint/6756

Actions (login required)

View Item View Item