A specific inducible nitric oxide inhibitor, ONO‐1714 attenuates inflammation‐related large bowel carcinogenesis in male Apc Min/+ mice

• Published in: International journal of cancer Vol. 121; no. 3; pp. 506 - 513
• Main Authors: Kohno, Hiroyuki, Takahashi, Mami, Yasui, Yumiko, Suzuki, Rikako, Miyamoto, Shingo, Kamanaka, Yoshihisa, Naka, Masao, Maruyama, Takayuki, Wakabayashi, Keiji, Tanaka, Takuji
• Format: Journal Article
• Language: English
• Published: 01.08.2007
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.22736

Abstract It is generally assumed that inflammation influences carcinogenesis. We previously reported that dextran sodium sulfate (DSS) strongly enhances colon carcinogenesis in the Apc Min/+ mice and the over‐expression of inducible nitric oxide synthase (iNOS) contributes to this enhancement. In the current study, we investigated the effect of a selective iNOS inhibitor, ONO‐1714 on colitis‐related colon carcinogenesis in the Apc Min/+ mouse treated with DSS. Male C57BL/6J Apc Min/+ and Apc +/+ mice were exposed to 1% DSS in their drinking water for 7 days. ONO‐1714 was given to the mice at a dose level of 50 or 100 ppm in diet for 5 weeks (during the administration of DSS). The tumor inhibitory effects by ONO‐1714 were assessed at week 5 by counting the incidence and multiplicity of colonic neoplasms. Additionally, we assessed serum lipid levels and colonic mRNA expression for cyclooxygenase (COX)‐2, iNOS, tumor necrosis factor (TNF)‐α and interleukin (IL)‐1β. Feeding with ONO‐1714 significantly inhibited the occurrence of colonic adenocarcinoma in a dose‐dependent manner in the Apc Min/+ mice. In addition, the treatment with ONO‐1714 significantly lowered the serum triglyceride levels and mRNA expression levels of COX‐2, TNFα and IL‐1β of colonic mucosa in the DSS‐treated Apc Min/+ mice. Neither ONO‐1714 nor DSS affected the colonic pathology in the Apc +/+ mice. Our findings may suggest that ONO‐1714 could therefore serve as an effective agent for suppression of colitis‐related colon cancer development in the Apc Min/+ mice. © 2007 Wiley‐Liss, Inc.