MT‐102 prevents tissue wasting and improves survival in a rat model of severe cancer cachexia

Journal of Cachexia, Sarcopenia and Muscle

Anika Tschirner¹  Stefan D. Anker¹  Jochen Springer¹  Junichi Ishida¹  Sandra Palus¹  Wolfram Doehner¹  Stephan vonHaehling²  Mareike S. Pötsch³ 

[1] Charite Medical School Berlin Institute of Health Center for Regenerative Therapies (BCRT) Berlin Germany;Department of Cardiology and Pneumology University Medicine Goettingen (UMG) Goettingen Germany;Institute of Pharmacology and Toxicology, Faculty of Medicine, Carl Gustav Carus Technische Universität Dresden Dresden Germany;

关键词: Cancer cachexia;    Animal model;    Drug development;    Muscle wasting;   

DOI  :  10.1002/jcsm.12537

来源: DOAJ

【 摘 要 】

Abstract Background Cachexia, a common manifestation of malignant cancer, is associated with wasting of skeletal muscle and fat tissue. In this study, we investigated the effects of a new first in class anabolic catabolic transforming agent on skeletal muscle in a rat model of cancer cachexia. Methods Young male Wistar Han rats were intraperitoneally inoculated with 108 Yoshida hepatoma AH‐130 cells and once daily treated with 0.3 mg kg−1, 3 mg kg−1 MT‐102, or placebo by gavage. Results Three mg kg−1d−1 MT‐102 not only prevented progressive loss of fat mass (−6 ± 2 g vs ‐12 ± 1 g; P < 0.001); lean mass (+1 ± 10 g vs. −37 ± 2 g; P < 0.001) and body weight (+1 ± 13 g vs. −60 ± 2 g; P < 0.001) were remained. Quality of life was also improved as indicated by a higher food intake 12.9 ± 3.1 g and 4.3 ± 0.5 g, 3 mg kg−1d−1 MT‐102 vs. placebo, respectively, P < 0.001) and a higher spontaneous activity (52 369 ± 6521 counts/24 h and 29 509 ± 1775 counts/24 h, 3 mg·kg‐1d‐1 MT‐102 vs. placebo, respectively, P < 0.01) on Day 11. Most importantly, survival was improved (HR = 0.29; 95% CI: 0.16–0.51, P < 0.001). The molecular mechanisms behind these effects involve reduction of overall protein degradation and activation of protein synthesis, assessed by measurement of proteasome and caspase‐6 activity or Western blot analysis, respectively. Conclusions The present study shows that 3 mg kg−1 MT‐102 reduces catabolism, while inducing anabolism in skeletal muscle leading to an improved survival.

【 授权许可】

Unknown