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- Title
A prostaglandin E2 receptor subtype EP1-selective antagonist, ONO-8711, suppresses 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis.
- Authors
Hiroki Makita; Michihiro Mutoh; Takayuki Maruyama; Kazuhiro Yonemoto; Atsushi Kobayashi; Hideki Fujitsuka; Makoto Toida; Toshiyuki Shibata; Shingo Miyamoto; Yumiko Yasui; Rikako Suzuki; Keiji Wakabayashi; Takuji Tanaka
- 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 E2 (PGE2) receptor EP1-selective antagonist ONO-8711 on 4-nitroquinoline 1-oxide (4-NQO)-induced oral carcinogenesis to know whether an EP1 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 PGE2 level and cell proliferation activity in the non-tumorous epithelium of the tongue. Also, treatment with ONO-8711 resulted in the decrease in EP1 immunohistochemical expression in the tongue lesions induced by 4-NQO. The results suggest that EP1 receptor involves in oral carcinogenesis, and that an EP1-selective antagonist ONO-8711 exerts the cancer chemopreventive effects through the suppression of EP1 expression, PGE2 biosynthesis and cell proliferation.
- Subjects
PROSTAGLANDINS; NITROQUINOLINE oxide; TONGUE cancer; CYCLOOXYGENASES
- Publication
Carcinogenesis, 2007, Vol 28, Issue 3, p677
- ISSN
0143-3334
- Publication type
Article