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: Makiko Kawaguchi, Ai Kanemaru, Tsuyoshi Fukushima, Koji Yamamoto, Hiroyuki Tanaka, Yukihiro Haruyama, Hiroshi Itoh, Nobuhiro Matsumoto, Kenji Kangawa, Masamitsu Nakazato, Hiroaki Kataoka
• Journal: Cancer science (Cancer Sci) Vol. 106 Issue 9 Pg. 1130-6 (Sep 2015) ISSN: 1349-7006 [Electronic] England
• PMID: 26094822 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Chemical References

• Carcinogens
• Ghrelin
• Dextran Sulfate
• Azoxymethane

Topics

• Animals
• Azoxymethane (toxicity)
• Carcinogenesis (chemically induced, drug effects, pathology)
• Carcinogens (toxicity)
• Colorectal Neoplasms (chemically induced, drug therapy, genetics, pathology)
• Dextran Sulfate (toxicity)
• Disease Models, Animal
• Ghrelin (administration & dosage, genetics)
• Inflammation (drug therapy, genetics, pathology)
• Male
• Mice
• Mice, Inbred C57BL