Inhibitory effect of a prostaglandin E receptor subtype EP(1) selective antagonist, ONO-8713, on development of azoxymethane-induced aberrant crypt foci in mice.
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| Abstract |
We previously reported that prostaglandin E(2) contributes to colon carcinogenesis through its binding to the prostaglandin E receptor subtype EP(1) using a genetic approach in EP(1)-knockout mice and a pharmacological approach with the EP(1) selective antagonist, ONO-8711. In the present study, we examined the effects of another more selective EP(1) receptor antagonist, ONO-8713, on development of azoxymethane (AOM)-induced aberrant crypt foci (ACFs) in male C57BL/6J mice treated i.p. with 10mg/kg body weight AOM once a week for 3weeks. Administration of ONO-8713 at doses of 250, 500 and 1000ppm in diet during and post-AOM treatment for 5weeks resulted in a dose-dependent reduction of ACF formation, being 15, 30 and 36% inhibition of the control value, respectively. The level of inhibition was similar to that with ONO-8711. Moreover, ONO-8713 suppressed the development of ACF when administered at post-AOM, as in the case of ONO-8711. The data confirm EP(1) receptor involvement in colon carcinogenesis.
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| Authors | K Watanabe, T Kawamori, S Nakatsugi, T Ohta, S Ohuchida, H Yamamoto, T Maruyama, K Kondo, S Narumiya, T Sugimura, K Wakabayashi |
| Journal | Cancer letters (Cancer Lett) Vol. 156 Issue 1 Pg. 57-61 (Aug 01 2000) ISSN: 0304-3835 [Print] Ireland |
| PMID | 10840160 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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