Exercise training delays cardiac remodeling in a mouse model of cancer cachexia

• Published in: Life sciences (1973) Vol. 260; pp. 118392 - 12
• Main Authors: Fernandes, L.G., Tobias, G.C., Paixão, A.O., Dourado, P.M., Voltarelli, V.A., Brum, P.C.
• Format: Journal Article
• Language: English
• Published: New York Elsevier Inc 01.11.2020; Elsevier BV
• Subjects: Adenocarcinoma; Aerobic exercise training; Atrophy; Autophagy; BNIP3 protein; Cachexia; Cancer; Cancer cachexia; Cardiac damage; Cardiac function; Collagen; Colon; Echocardiography; Ejection fraction; Exercise; Fibrosis; Fitness training programs; Homeostasis; Inflammation; Light microscopy; Mitochondria; Morphology; mRNA; Necrosis; Optical microscopy; Phagocytosis; Physical training; Proteins; Robustness; Structure-function relationships; Training; Transforming growth factor-b1; Treadmills; Tumors; Ventricle; Western blotting; Cancer cachexia; Aerobic exercise training; Inflammation; Cardiac damage; Fibrosis; Necrosis
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2020.118392

We aimed to investigate the impact of cancer cachexia and previous aerobic exercise training (AET) on cardiac function and structure in tumor bearing mice. Colon adenocarcinoma cells 26 (CT26) were subcutaneously injected in BALB/c mice to establish robust cancer cachexia model. AET was performed on a treadmill during 45 days, 60 min/5 days per week. Cardiac function was evaluated by echocardiography and cardiac morphology was assessed by light microscopy. The protein expression levels of mitochondrial complex were analyzed by Western blotting. The mRNA levels of genes related to cardiac remodeling and autophagy were analyzed by quantitative Real-Time PCR. Our data confirms CT26 tumor bearing mice as a well-characterized and robust model of cancer cachexia. CT26 mice exhibited cardiac remodeling and dysfunction characterized by cardiac atrophy and impaired left ventricle ejection fraction paralleled by cardiac necrosis, inflammation and fibrosis. AET partially reversed the left ventricle ejection fraction and led to significant anti-cardiac remodeling effect associated reduced necrosis, inflammation and cardiac collagen deposition in CT26 mice. Reduced TGF-β1 mRNA levels, increased mitochondrial complex IV protein levels and partial recovery of BNIP3 mRNA levels in cardiac tissue were associated with the cardiac effects of AET in CT26 mice. Thus, we suggest AET as a powerful regulator of key pathways involved in cardiac tissue homeostasis in cancer cachexia. Our study provides a robust model of cancer cachexia, as well as highlights the potential and integrative effects of AET as a preventive strategy for reducing cardiac damage in cancer cachexia.