Inhibitory effect of a prostaglandin E receptor subtype EP1 selective antagonist, ONO-8713, on development of azoxymethane-induced aberrant crypt foci in mice

We previously reported that prostaglandin E2 contributes to colon carcinogenesis through its binding to the prostaglandin E receptor subtype EP1 using a genetic approach in EP1-knockout mice and a pharmacological approach with the EP1 selective antagonist, ONO-8711. In the present study, we examined the effects of another more selective EP1 receptor antagonist, ONO-8713, on development of azoxymethane (AOM)-induced aberrant crypt foci (ACFs) in male C57BL/6J mice treated i.p. with 10 mg/kg body weight AOM once a week for 3 weeks. Administration of ONO-8713 at doses of 250, 500 and 1000 ppm in diet during and post-AOM treatment for 5 weeks 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 EP1 receptor involvement in colon carcinogenesis.