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Combined Exercise Training Positively Affects Muscle Wasting in Tumor-Bearing Mice


Medicine & Science in Sports & Exercise: July 2019 - Volume 51 - Issue 7 - p 1387–1395
doi: 10.1249/MSS.0000000000001916

Introduction Cancer cachexia is characterized by loss of muscle mass and function. Increased protein catabolism, inflammation, impaired anabolism, and mitochondrial function markedly contribute to the pathogenesis of this syndrome. Physical activity has been suggested as a useful tool to prevent or at least delay the onset and progression of cancer-induced muscle wasting. Two main types of exercise can be adopted, namely, resistance and endurance training. The present study is aimed to investigate the effectiveness of a combined (resistance + endurance) exercise protocol in preventing/reverting cancer-induced muscle wasting.

Methods Mice bearing the C26 colon carcinoma have been used as a model of cancer cachexia. They have been exposed to combined exercise training during 6 wk (4 before tumor implantation, 2 during tumor growth). Climbing a 1-m ladder inclined at 85° has been used for resistance training, while aerobic (endurance) exercise has been carried out on the same day using a motorized wheel.

Results In C26-bearing mice, both muscle mass and strength are improved by combined training, while just the latter increased in exercised healthy animals. Such a pattern is associated with modulations of two markers of autophagy, namely, LC3B-I/II ratio, increased in sedentary tumor hosts and reduced in exercised C26-bearing mice, and p62, steadily increased in both sedentary and trained tumor-bearing animals. Finally, combined training is not able to modify PGC-1α protein levels, but it improves succinate dehydrogenase activity, both reduced in the muscle of the C26 hosts.

Conclusion The data reported in the present study show that combined training improves muscle mass and function in the C26 hosts, likely modulating autophagy and improving mitochondrial function; these observations suggest that combined exercise might become part of a multimodal approach to treat cancer cachexia.

1Department of Clinical and Biological Sciences, University of Turin, Turin, ITALY;

2Physical Education and Sport Sciences Department, Tarbiat Modares University, Teheran, IRAN;

3Interuniversity Institute of Myology, Urbino, ITALY; and

4Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN

Address for correspondence: Paola Costelli, Department of Clinical and Biological Sciences, University of Turin, Corso Raffaello, 30, Turin 10125, Italy; E-mail:

K. R. and R. B. equally contributed to this work.

Submitted for publication June 2018.

Accepted for publication January 2019.

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Online date: February 5, 2019

© 2019 American College of Sports Medicine