Provision of rhIGF-I/IGFBP-3 complex attenuated development of cancer cachexia in an experimental tumor model

Tumor growth is associated with development of cachexia which includes progressive wasting and anorexia. Our previous studies have indicated that insulin like growth factor-I (rhlGF-I) in complex with its binding protein 3 (IGFBP 3), but not free IGF-I, was a potent stimulator of muscle protein synthesis in rats with chronic undernutrition. The aim of the present study was to evaluate the effect of rhlGF-I/IGFBP-3 on the development of cancer cachexia, and to assess safety data on net tumor growth and progression during treatment. Methods: A methylcholantrene induced sarcoma was implanted s.c. in C 57 bl mice. The animals were provided with rhlGF-I/rhlGFBP-3 (5 mu g/g bw) i.v. twice daily (n = 18). Controls were provided with saline (n = 20). Body weight and food intake were registered daily. Net tumor growth was measured over 10 days. Protein synthesis in liver and muscle, as well as plasma concentrations of glucose, insulin, IGF-I and amino acids were measured at the end of the study. Results: tumor size did not differ between control mice and rhlGF-I/rhlGFBP-3 treated mice (1.5 +/- 0.1 g wet tumor weight vs 1.6 +/- 0.2 g respectively). Saline treated tumor bearing controls lost 9.1 +/- 1.3 % body weight over 10 days due to rapid tumor growth while rhlGF-I/rhlGFBP-3 provision attenuated weight loss to 5.6 +/- 1.3% of body weight in study mice (P < 0.05). Food intake was improved and blood glucose concentration was reduced from 7.1 +/- 0.5 to 5.8 +/- 0.2 (P < 0.05) in response to treatment. Conclusion: Our results demonstrate that rhlGF-I/rhlGFBP-3 complex did not affect net tumor growth. Moreover rhlGF-I/rhlGFBP-3 complex improved tumor-host nutritional state by improving food intake, attenuating weight loss and improving glucose metabolism. (C) 2000 Harcourt Publishers Ltd.