NIH Public Access Author Manuscript Anticancer Res. Author manuscript; available in PMC 2014 December 01.

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Published in final edited form as: Anticancer Res. 2013 December ; 33(12): 5261–5271.

Soluble Epoxide Hydrolase Deficiency Inhibits Dextran Sulfate Sodium-induced Colitis and Carcinogenesis in Mice WANYING ZHANG#1, HAONAN LI#1, HUA DONG2, JIE LIAO1, BRUCE D. HAMMOCK2, and GUANG-YU YANG1 1Department

of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL,

U.S.A. 2Department

#

of Entomology, University of California, Davis, CA, U.S.A.

These authors contributed equally to this work.

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Abstract

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Soluble epoxide hydrolase (sEH) hydrolyses/inactivates anti-inflammatory epoxyeicosatrienoic acids (EETs) to their corresponding diols, and targeting sEH leads to strong anti-inflammatory effects. In the present study, using a tissue microarray and immunohistochemical approach, a significant increase of sEH expression was identified in ulcerative colitis (UC)-associated dysplasia and adenocarcinoma. The effects of deficiency in the sEH gene were determined on dextran sulfate sodium (DSS) colitis-induced carcinogenesis. The effects of EETs on lipopolysaccharide (LPS)-activated macrophages were analyzed in vitro. With extensive histopathological and immunohistochemical analyses, compared to wild-type mice, sEH−/− mice exhibited a significant decrease in tumor incidence (13/20 vs. 6/19, p