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

• DOI: 10.1371/journal.pone.0251942
• Publication Date: 2021-05-18T17:44:11Z
• Authors: Yohei Shirakami; Takayuki Nakanishi; Noritaka Ozawa; Takayasu Ideta; Takahiro Kochi; Masaya Kubota; Hiroyasu Sakai; Takashi Ibuka; Takuji Tanaka; Masahito Shimizu
• Keywords: 0301 basic medicine; Carcinogenesis; Science; Adenomatous Polyposis Coli Protein; Azoxymethane; Dinoprostone; 03 medical and health sciences; Animals; Humans; Chemokine CCL2; Cell Proliferation; Inflammation; Interleukin-6; Tumor Necrosis Factor-alpha; Q; Dextran Sulfate; R; Interleukin-18; Rats; 3. Good health; Gene Expression Regulation, Neoplastic; Benzamides; Colonic Neoplasms; Mutation; Medicine; Receptors, Prostaglandin E, EP4 Subtype; Research Article; Signal Transduction

Prostaglandin E2 receptor EP4 is involved in inflammation and related tumorigenesis the colorectum. This study aimed to investigate chemopreventive ability of RQ-15986, a selective antagonist, colitis-related colorectal tumorigenesis. Male Kyoto APC delta rats, which have mutations, were treated with azoxymethane dextran sulfate sodium subsequently administered RQ-15986 for eight weeks. At end experiment, development tumor was significantly inhibited RQ-15986-treated group. The cell proliferation crypts tumors colorectum decreased following treatment. also suppressed expression pro-inflammatory cytokines, including necrosis factor-α, interleukin-6, interleukin-18, monocyte chemotactic protein-1, colon mucosa. In addition, levels indoleamine 2,3-dioxygenase, immune tolerance, epithelium These findings indicate that inhibits colitis-associated by attenuating inflammation, suppressing proliferation, modulating 2,3-dioxygenase. Targeting prostaglandin E2/EP4 signaling might be useful strategy chemoprevention inflammation-related cancer.