title: Ghrelin administration suppresses inflammation-associated colorectal carcinogenesis in mice.
abstract: Ghrelin is a 28-amino-acid peptide that stimulates the release of pituitary growth hormone. Because of its orexigenic effects, ghrelin is being developed as a therapeutic option for postoperative support and treatment of anorexia-cachexia syndrome of cancer patients. However, ghrelin has a multiplicity of physiological functions, and it also affects cell proliferation. Therefore, the effects of ghrelin administration on carcinogenesis and cancer progression in patients susceptible to cancer should be clarified. In this study, we examined the effects of ghrelin on cancer promotion in vivo using murine intestinal carcinogenesis models. Intestinal tumorigenesis was examined to determine the effects of either exogenous ghrelin administration or ghrelin deficiency following deletion of the Ghrl gene. Two murine intestinal tumorigenesis models were used. The first was the azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced inflammation-associated colon carcinogenesis model and the second was the Apc(Min/+) genetic cancer susceptibility model. In AOM/DSS-treated mice, administration of ghrelin significantly suppressed tumor formation in the colon. In contrast, ghrelin administration did not affect the number of intestinal tumors formed in Apc(Min/+) mice. The absence of endogenous ghrelin did not affect the incidence of intestinal tumors in either AOM/DSS-treated mice or Apc(Min/+) mice, though tumor size tended to be larger in Ghrl(-/-) colons in the AOM/DSS model. No tumor-promoting effect was observed by ghrelin administration in either tumorigenesis model. In summary, this study provides in vivo experimental evidence for the usefulness of ghrelin administration in the chemoprevention of inflammation-associated colorectal carcinogenesis and may suggest its safety in patients under colitis-associated cancer susceptibility conditions.
authors.affiliation: Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Kawaguchi
authors.affiliation: Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Kanemaru
authors.affiliation: Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Fukushima
authors.affiliation: Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Haruyama
authors.affiliation: Department of Molecular Pathology, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Itoh
authors.affiliation: Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Matsumoto
authors.affiliation: Department of Biochemistry, National Cardiovascular Center Research Institute, Osaka, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kangawa
authors.affiliation: Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Nakazato
authors.affiliation: Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kataoka
mesh_terms: D000818:Animals; D001397:Azoxymethane / Q000633:toxicity; D063646:Carcinogenesis / Q000139:chemically induced / Q000187:drug effects* / Q000473:pathology; D002273:Carcinogens / Q000633:toxicity; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D054439:Ghrelin / Q000008:administration & dosage* / Q000235:genetics; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D002273:Carcinogens; D054439:Ghrelin; D016264:Dextran Sulfate; D001397:Azoxymethane
keywords: Carcinogenesis; colon cancer; ghrelin; mouse model; ulcerative colitis