Abstract
Abstract Soluble epoxide hydrolase (sEH) can quickly inactivate epoxyeicosatrienoic acids (EETs) anti-inflammatory function via converting it to dihydroxyeicosatrienoic acid (DHETs). Inhibition of sEH has shown effects against inflammation. But little is studied about the effect of sEH on colitis-induced carcinogenesis. In this study, we determined the role of sEH gene deficiency in suppressing the development of colitis-induced tumor using chronic colitis mouse model in IL-10 knockout mice combined with sEH gene deficiency. Tumor formation in the bowel was examined at age of 25 weeks for male mice and 35 weeks for female mice. Our results showed that sEH (-/-)/IL-10 (-/-) mice exhibited a significant decrease of tumor multiplicity (2 tumor/mouse vs. 1 tumor/mouse) and tumor size (344.55±71.73 vs. 126.94±23.18 mm3, p=0.028) as compared to IL-10(-/-) mice. But no difference was observed for tumor incidence. Colitis-induced dysplasia was further identified by Ki67-labeled luminal surface epithelial cell proliferation combined with morphologic features and revealed that the number of dysplasia was significantly decreased in sEH (-/-)/IL-10 (-/-) mice. Histopathological analysis of inflammatory activity in the bowel showed the significantly lower inflammation scores, including inflammation-involved area (1.4±0.18 vs. 0.70±0.16, P=0.007), ulcer (2.15±0.18 vs. 1.55±0.35, P=0.032), and myeloperoxidase-labeled inflammatory cell infiltrates in sEH (-/-)/ IL-10(-/-) mice compared to IL-10(-/-) mice. qPCR and western blotting assays showed a downregulation of inflammatory cytokines and NF-kB signals. Analysis of eicsanoid acid metabolic profile confirmed sEH functional deficiency and showed a significant increase in the ratios of EETs/DHET and EpOME/DiOME in sEH (-/-)/IL-10 (-/-) mice compared to IL-10(-/-) mice. The results indicate that sEH gene plays an important role in the development of chronic colitis-induced carcinoma and could serve as a crucial target of cancer chemoprevention. (Supported by NIH R01 grant CA137467) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1006. doi:1538-7445.AM2012-1006
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
