Anti-cachectic effect of ghrelin in nude mice bearing human melanoma cells.
Ghrelin is a novel brain-gut peptide that stimulates food intake and body weight gain. We studied the anabolic effect of ghrelin in a cancer cachexia mouse model. SEKI, a human melanoma cell line, was inoculated into nude mice to examine the effects of ghrelin on food intake and body weight. The intraperitoneal administration of ghrelin twice a day (6 nmol/mice/day) for 6 days suppressed weight loss in SEKI-inoculated mice and increased the rate of weight gain in vehicle-treated nude mice. Ghrelin administration also increased food intake in both SEKI- and vehicle-treated mice. Both the weight of white adipose tissue and the plasma leptin concentration were reduced in tumor-inoculated mice compared with vehicle-treated mice; these factors increased following ghrelin administration. The levels of both ghrelin peptide and mRNA in the stomach were upregulated in tumor-inoculated mice. The anabolic effect of ghrelin efficiently reverses the cachexia in mice bearing SEKI human melanoma. Ghrelin therefore may have a therapeutic ability to ameliorate cancer cachexia.
Hanada
Takeshi
T
Third Department of Internal Medicine, Miyazaki Medical College, Miyazaki 889-1692, Japan.
Toshinai
Koji
K
Kajimura
Naoko
N
Nara-Ashizawa
Noriko
N
Tsukada
Toshihiko
T
Hayashi
Yujiro
Y
Osuye
Kazuhiro
K
Kangawa
Kenji
K
Matsukura
Shigeru
S
Nakazato
Masamitsu
M
D000818:Animals; D001835:Body Weight; D002100:Cachexia; D017690:Cell Transplantation; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D054439:Ghrelin; D006131:Growth Inhibitors / Q000097:blood; D006801:Humans; D007274:Injections, Intraperitoneal; D015850:Interleukin-6; D020738:Leptin / Q000097:blood; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000097:blood; D008545:Melanoma / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000503:physiopathology; D036361:Peptide Hormones / Q000008:administration & dosage / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D054439:Ghrelin; D006131:Growth Inhibitors; D015850:Interleukin-6; C507837:LIF protein, human; D020738:Leptin; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D036361:Peptide Hormones