Suppression of azoxymethane‐induced colon cancer development in rats by a prostaglandin E receptor EP1‐selective antagonist

• Published in: Cancer science 2005-05, Vol.96 (5), p.260-264
• Main Authors: Niho, Naoko, Mutoh, Michihiro, Kitamura, Tomohiro, Takahashi, Mami, Sato, Hidetaka, Yamamoto, Hiroshi, Maruyama, Takayuki, Ohuchida, Shuichi, Sugimura, Takashi, Wakabayashi, Keiji
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; Azoxymethane - pharmacology; Biological and medical sciences; Bridged Bicyclo Compounds - pharmacology; Bridged Bicyclo Compounds - therapeutic use; Caproates - pharmacology; Caproates - therapeutic use; Colonic Neoplasms - chemically induced; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; Colonic Neoplasms - prevention & control; Gastroenterology. Liver. Pancreas. Abdomen; Male; Medical sciences; Original; Rats; Rats, Inbred F344; Receptors, Prostaglandin E - antagonists & inhibitors; Receptors, Prostaglandin E - metabolism; Receptors, Prostaglandin E, EP1 Subtype; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/j.1349-7006.2005.00047.x

Prostaglandin E2 is involved in colon carcinogenesis through its binding to the PGE2 receptor subtypes EP1, EP2, EP3 and EP4. We have demonstrated that administration of ONO‐8711, an EP1‐selective antagonist, suppresses development of AOM‐induced ACF in C57BL/6 mice and F344 rats. ONO‐8711 also reduced the numbers of intestinal polyps in Min mice. In the present study, we investigated the long‐term effects of ONO‐8711 on colon cancer development in rats treated with AOM. Male F344 rats were injected subcutaneously with AOM (15 mg/kg body weight) once a week for the first 2 weeks to develop colon cancer. Administration of 400 or 800 p.p.m. ONO‐8711 in their diets for 32 weeks reduced the incidence, multiplicity and volume of colon carcinomas. The incidence of colon adenocarcinomas in AOM‐treated rats was 97, 83 and 76% (P