Abstract
Cachexia is a wasting syndrome associated with cancer, AIDS, and systemic inflammatory diseases. It is characterized by dramatic weight loss, food intake reduction, and skeletal muscle atrophy. Specific strategies to exert ameliorative effects on cachectic status have not been contrived. Ghrelin is an orexigenic peptide produced predominantly in the stomach. Ghrelin acts on the hypothalamus and the pituitary gland, induces growth hormone secretion and stimulates food intake through binding to its receptor, growth hormone secretagogue receptor (GHS-R). We reported that urethane-induced lung carcinogenesis highly occurred in the lung epithelium-specific Pten-deleted (Pten-KO) mice. To investigate the pharmacological potential of ghrelin for the treatment of lung cancer-induced cachexia, we administered urethane intraperitoneally to the 10-week-old Pten-KO mice and their wild mice. Ghrelin 10 nmol/mouse or PBS was given to Pten-KO mice intraperitoneally twice daily for 4 weeks starting from 28 weeks after administration of urethane. Reduction of food intake, body weight loss, and gastrocnemius muscle weight loss of Pten-KO mice were severer than those of wild-type controls at 28 weeks after urethane administration. Ghrelin-treated Pten-KO mice had smaller reductions of food intake, body weight, and muscle weight than PBS-treated Pten-KO mice. The intramuscular expression levels of MuRF-1 and Atragin-1, both of which were the markers of skeletal muscle catabolism of ghrelin-treated Pten-KO mice were significantly lower than those of PBS-treated Pten-KO mice. These results indicate that ghrelin administration exerts a therapeutic potential for cancer-induced cachexia in mice.
- © 2013 ERS
