Inhibitory effect of a prostaglandin E receptor subtype EP(1) selective antagonist, ONO-8713, on development of azoxymethane-induced aberrant crypt foci in mice

Cancer Lett. 2000 Aug 1;156(1):57-61. doi: 10.1016/s0304-3835(00)00440-7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Antineoplastic Agents / therapeutic use*
  • Azoxymethane
  • Cinnamates / therapeutic use*
  • Colonic Neoplasms / chemically induced
  • Colonic Neoplasms / prevention & control*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Precancerous Conditions / chemically induced
  • Precancerous Conditions / prevention & control*
  • Receptors, Prostaglandin E / antagonists & inhibitors*
  • Receptors, Prostaglandin E / physiology
  • Receptors, Prostaglandin E, EP1 Subtype

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antineoplastic Agents
  • Cinnamates
  • ONO 8713
  • Ptger1 protein, mouse
  • Receptors, Prostaglandin E
  • Receptors, Prostaglandin E, EP1 Subtype
  • Azoxymethane