| RRC ID |
2817
|
| Author |
Makita H, Mutoh M, Maruyama T, Yonemoto K, Kobayashi A, Fujitsuka H, Toida M, Shibata T, Miyamoto S, Yasui Y, Suzuki R, Wakabayashi K, Tanaka T.
|
| Title |
A prostaglandin E2 receptor subtype EP1-selective antagonist, ONO-8711, suppresses 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis.
|
| Journal |
Carcinogenesis
|
| Abstract |
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.
|
| Volume |
28(3)
|
| Pages |
677-84
|
| Published |
2007-3-1
|
| DOI |
10.1093/carcin/bgl178
|
| PII |
bgl178
|
| PMID |
17052996
|
| MeSH |
4-Nitroquinoline-1-oxide / toxicity*
Animal Feed
Animals
Bridged Bicyclo Compounds / pharmacology*
Caproates / pharmacology*
Carcinogens / toxicity
Carcinoma, Squamous Cell / chemically induced
Carcinoma, Squamous Cell / pathology
Carcinoma, Squamous Cell / prevention & control
Dinoprostone / metabolism
Male
Precancerous Conditions / chemically induced
Precancerous Conditions / pathology
Precancerous Conditions / prevention & control
Rats
Rats, Inbred F344
Receptors, Prostaglandin E / antagonists & inhibitors*
Tongue / metabolism
Tongue Neoplasms / chemically induced*
Tongue Neoplasms / pathology
Tongue Neoplasms / prevention & control*
|
| IF |
4.603
|
| Times Cited |
17
|
|
WOS Category
|
ONCOLOGY
|
| Resource |
| Rats |
F344/DuCrlCrlj(strainID=537) |
