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

Amini-Khoei, Hossein, Momeny, Majid, Abdollahi, Alireza, Dehpour, Ahmad Reza, Amiri, Shayan, Haj-Mirzaian, Arya, Tavangar, Seyed Mohammad, Ghaffari, Seyed Hamid, Rahimian, Reza and Mehr, Shahram Ejtemaei (2016) Tropisetron suppresses colitis-associated cancer in a mouse model in the remission stage. International Immunopharmacology, 36 9-16. doi:10.1016/j.intimp.2016.04.014


Author Amini-Khoei, Hossein
Momeny, Majid
Abdollahi, Alireza
Dehpour, Ahmad Reza
Amiri, Shayan
Haj-Mirzaian, Arya
Tavangar, Seyed Mohammad
Ghaffari, Seyed Hamid
Rahimian, Reza
Mehr, Shahram Ejtemaei
Title Tropisetron suppresses colitis-associated cancer in a mouse model in the remission stage
Journal name International Immunopharmacology   Check publisher's open access policy
ISSN 1878-1705
1567-5769
Publication date 2016-07-01
Year available 2016
Sub-type Article (original research)
DOI 10.1016/j.intimp.2016.04.014
Open Access Status Not yet assessed
Volume 36
Start page 9
End page 16
Total pages 8
Place of publication London, United Kingdom
Publisher Elsevier
Collection year 2017
Language eng
Formatted 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.
Keyword 5-HT3 receptor
CAC
Colitis
Serotonin
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
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