Suppression of azoxymethane-induced colon cancer development in rats by a prostaglandin E receptor EP1-selective antagonist
Corresponding Author
Naoko Niho
Cancer Prevention Basic Research Project, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045,
To whom correspondence should be addressed. E-mail: [email protected]Search for more papers by this authorMichihiro Mutoh
Cancer Prevention Basic Research Project, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045,
Search for more papers by this authorTomohiro Kitamura
Cancer Prevention Basic Research Project, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045,
Search for more papers by this authorMami Takahashi
Cancer Prevention Basic Research Project, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045,
Search for more papers by this authorHidetaka Sato
Department of Biological Safety Research, Japan Food Research Laboratories, 3 Bunkyo, 2-chome, Chitose-shi, Hokkaido 066-0052
Search for more papers by this authorHiroshi Yamamoto
Minase Research Institute, Ono Pharmaceutical Co., 3-1-1 Sakurai, Shimamoto-cho, Mishima-gun, Osaka 618-8585 Japan
Search for more papers by this authorTakayuki Maruyama
Minase Research Institute, Ono Pharmaceutical Co., 3-1-1 Sakurai, Shimamoto-cho, Mishima-gun, Osaka 618-8585 Japan
Search for more papers by this authorShuichi Ohuchida
Minase Research Institute, Ono Pharmaceutical Co., 3-1-1 Sakurai, Shimamoto-cho, Mishima-gun, Osaka 618-8585 Japan
Search for more papers by this authorTakashi Sugimura
Cancer Prevention Basic Research Project, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045,
Search for more papers by this authorKeiji Wakabayashi
Cancer Prevention Basic Research Project, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045,
Search for more papers by this authorCorresponding Author
Naoko Niho
Cancer Prevention Basic Research Project, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045,
To whom correspondence should be addressed. E-mail: [email protected]Search for more papers by this authorMichihiro Mutoh
Cancer Prevention Basic Research Project, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045,
Search for more papers by this authorTomohiro Kitamura
Cancer Prevention Basic Research Project, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045,
Search for more papers by this authorMami Takahashi
Cancer Prevention Basic Research Project, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045,
Search for more papers by this authorHidetaka Sato
Department of Biological Safety Research, Japan Food Research Laboratories, 3 Bunkyo, 2-chome, Chitose-shi, Hokkaido 066-0052
Search for more papers by this authorHiroshi Yamamoto
Minase Research Institute, Ono Pharmaceutical Co., 3-1-1 Sakurai, Shimamoto-cho, Mishima-gun, Osaka 618-8585 Japan
Search for more papers by this authorTakayuki Maruyama
Minase Research Institute, Ono Pharmaceutical Co., 3-1-1 Sakurai, Shimamoto-cho, Mishima-gun, Osaka 618-8585 Japan
Search for more papers by this authorShuichi Ohuchida
Minase Research Institute, Ono Pharmaceutical Co., 3-1-1 Sakurai, Shimamoto-cho, Mishima-gun, Osaka 618-8585 Japan
Search for more papers by this authorTakashi Sugimura
Cancer Prevention Basic Research Project, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045,
Search for more papers by this authorKeiji Wakabayashi
Cancer Prevention Basic Research Project, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045,
Search for more papers by this authorAbstract
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 < 0.05) in the 0, 400 and 800 p.p.m. of ONO-8711 groups, respectively. The multiplicity of adenocarcinomas was also decreased significantly, being 3.31 ± 0.33, 2.34 ± 0.27 (P < 0.05) and 2.06 ± 0.34 (P < 0.01) with 0, 400 and 800 p.p.m. of ONO-8711, respectively. Moreover, treatment with 800 p.p.m. ONO-8711 reduced the mean volume of adenocarcinomas to 49% (P < 0.05) of the value for the AOM treatment alone. Furthermore, the BrdU labeling index was decreased significantly in colon cancer cells by 800 p.p.m. ONO-8711. These results confirm that EP1 is involved in colon carcinogenesis and that EP1-selective antagonists might be promising candidates for colon cancer chemopreventive agents. (Cancer Sci 2005; 96: 260 –264)
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