Inhibitory effects of a selective prostaglandin E2 receptor antagonist RQ-15986 on inflammation-related colon tumorigenesis in APC-mutant rats.

Prostaglandin E2 receptor EP4 is involved in inflammation and related tumorigenesis in the colorectum. This study aimed to investigate the chemopreventive ability of RQ-15986, a selective EP4 antagonist, in colitis-related colorectal tumorigenesis. Male Kyoto APC delta rats, which have APC mutations...

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Autores principales:	Yohei Shirakami, Takayuki Nakanishi, Noritaka Ozawa, Takayasu Ideta, Takahiro Kochi, Masaya Kubota, Hiroyasu Sakai, Takashi Ibuka, Takuji Tanaka, Masahito Shimizu
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/632ca27268e34ffbae3aa9cd0de6aa1e
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spelling	oai:doaj.org-article:632ca27268e34ffbae3aa9cd0de6aa1e2021-11-25T06:19:08ZInhibitory effects of a selective prostaglandin E2 receptor antagonist RQ-15986 on inflammation-related colon tumorigenesis in APC-mutant rats.1932-620310.1371/journal.pone.0251942https://doaj.org/article/632ca27268e34ffbae3aa9cd0de6aa1e2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0251942https://doaj.org/toc/1932-6203Prostaglandin E2 receptor EP4 is involved in inflammation and related tumorigenesis in the colorectum. This study aimed to investigate the chemopreventive ability of RQ-15986, a selective EP4 antagonist, in colitis-related colorectal tumorigenesis. Male Kyoto APC delta rats, which have APC mutations, were treated with azoxymethane and dextran sulfate sodium and subsequently administered RQ-15986 for eight weeks. At the end of the experiment, the development of colorectal tumor was significantly inhibited in the RQ-15986-treated group. The cell proliferation of the crypts and tumors in the colorectum was decreased following RQ-15986 treatment. RQ-15986 also suppressed the expression of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-6, interleukin-18, and monocyte chemotactic protein-1, in the colon mucosa. In addition, the expression levels of indoleamine 2,3-dioxygenase, which is involved in immune tolerance, were decreased in the colorectal epithelium and tumors of the RQ-15986-treated group. These findings indicate that RQ-15986 inhibits colitis-associated colorectal tumorigenesis by attenuating inflammation, suppressing cell proliferation, and modulating the expression of indoleamine 2,3-dioxygenase. Targeting prostaglandin E2/EP4 signaling might be a useful strategy for chemoprevention of inflammation-related colorectal cancer.Yohei ShirakamiTakayuki NakanishiNoritaka OzawaTakayasu IdetaTakahiro KochiMasaya KubotaHiroyasu SakaiTakashi IbukaTakuji TanakaMasahito ShimizuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 5, p e0251942 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yohei Shirakami Takayuki Nakanishi Noritaka Ozawa Takayasu Ideta Takahiro Kochi Masaya Kubota Hiroyasu Sakai Takashi Ibuka Takuji Tanaka Masahito Shimizu Inhibitory effects of a selective prostaglandin E2 receptor antagonist RQ-15986 on inflammation-related colon tumorigenesis in APC-mutant rats.
description	Prostaglandin E2 receptor EP4 is involved in inflammation and related tumorigenesis in the colorectum. This study aimed to investigate the chemopreventive ability of RQ-15986, a selective EP4 antagonist, in colitis-related colorectal tumorigenesis. Male Kyoto APC delta rats, which have APC mutations, were treated with azoxymethane and dextran sulfate sodium and subsequently administered RQ-15986 for eight weeks. At the end of the experiment, the development of colorectal tumor was significantly inhibited in the RQ-15986-treated group. The cell proliferation of the crypts and tumors in the colorectum was decreased following RQ-15986 treatment. RQ-15986 also suppressed the expression of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-6, interleukin-18, and monocyte chemotactic protein-1, in the colon mucosa. In addition, the expression levels of indoleamine 2,3-dioxygenase, which is involved in immune tolerance, were decreased in the colorectal epithelium and tumors of the RQ-15986-treated group. These findings indicate that RQ-15986 inhibits colitis-associated colorectal tumorigenesis by attenuating inflammation, suppressing cell proliferation, and modulating the expression of indoleamine 2,3-dioxygenase. Targeting prostaglandin E2/EP4 signaling might be a useful strategy for chemoprevention of inflammation-related colorectal cancer.
format	article
author	Yohei Shirakami Takayuki Nakanishi Noritaka Ozawa Takayasu Ideta Takahiro Kochi Masaya Kubota Hiroyasu Sakai Takashi Ibuka Takuji Tanaka Masahito Shimizu
author_facet	Yohei Shirakami Takayuki Nakanishi Noritaka Ozawa Takayasu Ideta Takahiro Kochi Masaya Kubota Hiroyasu Sakai Takashi Ibuka Takuji Tanaka Masahito Shimizu
author_sort	Yohei Shirakami
title	Inhibitory effects of a selective prostaglandin E2 receptor antagonist RQ-15986 on inflammation-related colon tumorigenesis in APC-mutant rats.
title_short	Inhibitory effects of a selective prostaglandin E2 receptor antagonist RQ-15986 on inflammation-related colon tumorigenesis in APC-mutant rats.
title_full	Inhibitory effects of a selective prostaglandin E2 receptor antagonist RQ-15986 on inflammation-related colon tumorigenesis in APC-mutant rats.
title_fullStr	Inhibitory effects of a selective prostaglandin E2 receptor antagonist RQ-15986 on inflammation-related colon tumorigenesis in APC-mutant rats.
title_full_unstemmed	Inhibitory effects of a selective prostaglandin E2 receptor antagonist RQ-15986 on inflammation-related colon tumorigenesis in APC-mutant rats.
title_sort	inhibitory effects of a selective prostaglandin e2 receptor antagonist rq-15986 on inflammation-related colon tumorigenesis in apc-mutant rats.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/632ca27268e34ffbae3aa9cd0de6aa1e
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Inhibitory effects of a selective prostaglandin E2 receptor antagonist RQ-15986 on inflammation-related colon tumorigenesis in APC-mutant rats.

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