IGF-1 treatment reduces weight loss and improves outcome in a rat model of cancer cachexia

Abstract

Background

A hallmark symptom of cancer cachexia is the loss of skeletal muscle. This is at least partially due to a deregulation of the growth hormone/IGF-1 axis and a subsequently impaired protein synthesis in skeletal muscle. Here, we investigated the effect of IGF-1 supplementation in a rat model of cancer cachexia.

Methods

Juvenile rats were inoculated with the Yoshida AH-130 hepatoma and treated once daily with 0.3 mg kg ⁻¹ day ⁻¹ (low dose) or 3 mg kg ⁻¹ day ⁻¹ (high dose) IGF-1 or placebo for a period of maximal 16 days. Body weight and body composition (by NMR) were assessed at baseline and at the end of the study or day of death. Locomotor activity and food intake were assessed at baseline and day 10/11 after tumour inoculation for 24 h.

Results

Untreated tumour-bearing rats lost 55.3 ± 2.14 g body weight, which was reduced by low-dose to −39.6 ± 11.1 g ( p = 0.0434) and high-dose IGF-1 to −42.7 ± 8.8 g ( p = 0.057). Placebo-treated rats lost 41.4 ± 2.0-g lean mass, which was attenuated by low-dose IGF-1 (−28.8 ± 8.3 g, p = 0.041) and high-dose IGF-1 (−30.9 ± 7.4, p = 0.067). Spontaneous activity and food intake were improved by low-dose IGF-1 only. No effect on fat mass was observed. Low-dose IGF-1 significantly reduced mortality (HR = 0.45, 95%CI = 0.21–0.93, p = 0.0315), whilst the high dose did not reach significance (HR = 0.68, 95%CI = 0.26–1.74, p = 0.42).

Conclusion

Low-dose IGF-1 reduced mortality and attenuated loss of body weight as well as muscle mass in the Yoshida hepatoma rat model. Moreover, an improved quality of life was observed in these animals. Further experiments using different doses are necessary.