ono-8711 and Tongue-Neoplasms

We previously reported that certain cyclooxygenase (COX) inhibitors could inhibit chemically induced tongue carcinogenesis. In the present study, we investigated the effects of prostaglandin E(2) (PGE(2)) receptor EP(1)-selective antagonist ONO-8711 on 4-nitroquinoline 1-oxide (4-NQO)-induced oral carcinogenesis to know whether an EP(1) receptor involves in oral carcinogenesis. Male Fischer 344 rats were given drinking water containing 4-NQO for 8 weeks (20 p.p.m. for the initial 2 weeks, 25 p.p.m. for 2 weeks, and then 30 p.p.m. for 4 weeks). After 4-NQO treatment, animals were given 400 or 800 p.p.m. ONO-8711 containing diets for 23 weeks. The incidence of tongue squamous cell carcinomas (SCC) in the 4-NQO-treated rats was 64%, while that in the rats given ONO-8711 after 4-NQO exposure was 29 (P<0.05) and 29% (P<0.05) in the 400 and 800 p.p.m. of ONO-8711, respectively. The multiplicity of tongue cancer was also smaller in the 4-NQO + ONO-8711 (400 p.p.m. ONO-8711, 0.35 +/- 0.61; and 800 p.p.m. ONO-8711, 0.29 +/- 0.47; P<0.05), when compared with the 4-NQO alone group (0.88 +/- 0.88). Feeding with ONO-8711 significantly reduced PGE(2) level and cell proliferation activity in the non-tumorous epithelium of the tongue. Also, treatment with ONO-8711 resulted in the decrease in EP(1) immunohistochemical expression in the tongue lesions induced by 4-NQO. The results suggest that EP(1) receptor involves in oral carcinogenesis, and that an EP1-selective antagonist ONO-8711 exerts the cancer chemopreventive effects through the suppression of EP(1) expression, PGE(2) biosynthesis and cell proliferation.

Topics: 4-Nitroquinoline-1-oxide; Animal Feed; Animals; Bridged Bicyclo Compounds; Caproates; Carcinogens; Carcinoma, Squamous Cell; Dinoprostone; Male; Precancerous Conditions; Rats; Rats, Inbred F344; Receptors, Prostaglandin E; Tongue; Tongue Neoplasms