Abstract LB-4: Ghrelin administration suppresses inflammation-associated colorectal carcinogenesis in mice

Abstract

Abstract Background and aim: Ghrelin is a 28-amino-acid peptide, capable of stimulating growth hormone release. Because of its orexigenic effect, ghrelin is being developed as a therapeutic option for post-operative support and anorexia-cachexia syndrome of cancer patients. However, ghrelin has a multiplicity of physiological functions in various organs and immune system, and also affects cell proliferation. Therefore, it is important to know the effect of ghrelin administration on carcinogenesis and cancer progression in patients who are susceptible to cancer. This study aimed to test the effect of ghrelin on cancer promotion using murine intestinal carcinogenesis models. Method: Effect of ghrelin knockout or exogenous ghrelin administration (3 nmoles/day, i.p.) on intestinal tumorigenesis was analyzed in two types of murine intestinal tumorigenesis models; ApcMin/+ mice (genetic cancer susceptibility model) and AOM/DSS-treated mice (inflammation-associated colon cancer model). Results: The absence of ghrelin did not affect the number of intestinal tumors formed in ApcMin/+ mice and AOM/DSS-treated mice. Administration of ghrelin did not affect the number of intestinal tumors formed in ApcMin/+ mice, either. However, in AOM/DSS-treated mice, the administration of ghrelin significantly suppressed the formation of colon tumors (p < 0.001). The intestinal mRNA levels of inflammatory cytokines after DSS treatment were also suppressed by the administration of ghrelin. Conclusion: Ghrelin administration suppresses inflammation-associated colorectal carcinogenesis, which is possibly mediated by anti-inflammatory effects of ghrelin. Citation Format: Hiroaki Kataoka, Makiko Kawaguchi, Ai Kanemaru, Tsuyoshi Fukushima, Nobuhiro Matsumoto, Masamitsu Nakazato. Ghrelin administration suppresses inflammation-associated colorectal carcinogenesis in mice. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-4. doi:10.1158/1538-7445.AM2014-LB-4