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Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Nov 7, 2008; 14(41): 6303-6305
Published online Nov 7, 2008. doi: 10.3748/wjg.14.6303
Growth hormone releasing peptide 2 reverses anorexia associated with chemotherapy with 5-fluorouracil in colon cancer cell-bearing mice
Simona Perboni, Cyril Bowers, Shinya Kojima, Akihiro Asakawa, Akio Inui
Simona Perboni, Unità Operativa Day Hospital Area Medica, Azienda Ospedaliera di Desenzano sul Garda, Ospedale di Manerbio, I-25025 Brescia, Italy
Cyril Bowers, Tulane University, Health Science Center, New Orleans, Louisiana 70112, United States
Shinya Kojima, Akihiro Asakawa, Akio Inui, Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, 890-8520, Japan
Author contributions: Asakawa A, Bowers C, and Inui A designed research; Perboni S and Kojima S performed research; Perboni A wrote the paper.
Supported by (in part) A Grant-in-Aid for Scientic Research (B:16390208) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (to A.I.)
Correspondence to: Akio Inui, MD, PhD, Professor and Chairman, Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragtaoka, Kagoshima 890-8520, Japan. inui@m.kufm.kagoshima-u.ac.jp
Telephone: +81-99-2755748 Fax: +81-99-2755748
Received: October 15, 2008
Revised: October 30, 2008
Accepted: November 6, 2008
Published online: November 7, 2008
Abstract

The cancer-associated anorexia-cachexia syndrome is observed in 80% of patients with advanced-stage cancer, and is one of the major obstacles in chemotherapy. Ghrelin is a orexigenic hormone that has been proposed to prevent anorexia. Aim of the study was to determine whether the addition of the ghrelin agonist growth hormone releasing peptide 2 (GHRP-2) to cytotoxic therapy with 5-fluorouracil (5-FU) prevents the anorexia associated with chemotherapy in cancer cachectic mice. Thirty-three BALB/c female tumour-bearing mice were randomized to receive a solution containing: (a) placebo; (b) GHRP-2; (c) 5-FU; or (d) 5-FU + GHRP-2. Ten BALB/c no tumour-bearing mice received placebo solution. Food intake and survival were checked. Six hours after the drug injection the cumulative food intake was significantly increased in mice treated with the combination of 5-FU + GHRP-2 versus the 5-FU alone (P = 0.0096). On day 3, the cumulative food intake of mice treated with GHRP-2, 5-FU and 5-FU + GHRP-2 significantly increased compared with naive and vehicle groups (P = 0.0007, P = 0.0038 and P = 0.0166, respectively). The median survival time was longer in 5-FU + GHRP-2 treated mice than in those with 5-FU, although it was not significant (18 d versus 15.5 d, P = 0.7). For the first time, we demonstrated that the addition of GHRP-2 to cytotoxic therapy with 5-FU improved appetite in tumour-bearing mice with anorexia/cachexia syndrome in early stage. These data suggest that GHRP-2 may improve the efficacy of therapy and the quality of life of cancer patients thank to the amelioration of their nutritional state.

Keywords: GHS; Ghrelin; Cancer anorexia-cachexia syndrome; Food intake; Chemotherapy; Colon cancer cell line; Murine model