Inhibitory effect of a prostaglandin E receptor subtype EP(1) selective antagonist, ONO-8713, on development of azoxymethane-induced aberrant crypt foci in mice.
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.
Watanabe
K
K
Cancer Prevention Division, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, 104-0045, Tokyo, Japan.
Kawamori
T
T
Nakatsugi
S
S
Ohta
T
T
Ohuchida
S
S
Yamamoto
H
H
Maruyama
T
T
Kondo
K
K
Narumiya
S
S
Sugimura
T
T
Wakabayashi
K
K
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001397:Azoxymethane; D002934:Cinnamates / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011230:Precancerous Conditions / Q000139:chemically induced / Q000517:prevention & control*; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors* / Q000502:physiology; D058306:Receptors, Prostaglandin E, EP1 Subtype
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D002934:Cinnamates; C411295:ONO 8713; C545636:Ptger1 protein, mouse; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D001397:Azoxymethane