Preconditioning Exercise Protects Against Tumor-Mediated Muscle Dysfunction in the Male Mouse

BACKGROUND: Cancer is associated with cardiac and skeletal muscle wasting. While exercise has been shown to be myoprotective, less is known about the most effective "dose" of exercise in terms of intensity, timing, and duration. Therefore, the purpose of this study was to determine the effects of preconditioning exercise - exercise completedJ before tumor bearing - as a protective measure for tumor-mediated muscle wasting. METHODS: Male mice were randomly separated into four groups: sedentary non-tumor bearing (SED+NT), sedentary tumor bearing (SED+T), treadmill exercise non-tumor bearing (TM+NT), and treadmill exercise tumor bearing (TM+T). Mice underwent an 8-week progressive treadmill exercise training protocol (TM) or remained sedentary (SED). At the end of the preconditioning treadmill training protocol, mice remained sedentary for 4 weeks. During this 4 week sedentary period, mice were implanted with tumor cells (T group; 1x105 LLC cells in flank) or remained non-tumor (NT). To determine whether 8 weeks of exercise preconditioning could preserve cardiac and skeletal muscle function, mice underwent echocardiogram and grip strength analyses at baseline, 8-week, and 12-week time points. RESULTS: Tumor bearing resulted in significant muscle dysfunction. SED+T showed a significant decrease in fractional shortening (p<0.05) and grip strength (p<0.05) when compared to all other groups. This coincided with SED+T's significantly smaller heart masses and skeletal masses (p<0.05 vs to all other groups). Interestingly, preconditioning exercise (exercise prior to tumor bearing) appeared to offer myoprotection since TM groups were not significantly different from SED+NT for fractional shortening and grip strength (p>0.05). This data was in step with preserved heart mass and skeletal muscle mass in TM+T (p>0.05 vs SED+NT). CONCLUSION: These data indicate that exercise initiated prior to tumor bearing can protect the musculature from tumor-mediated muscle dysfunction. This may be attributed to slowed muscle wasting as evidenced by maintenance of muscle mass in TM+T groups. These data make an important case for the long-term benefits of an active lifestyle that last even after exercise is stopped (i.e., upon diagnosis and treatment). Such information is critical in elucidating the most effective "dose" of exercise for cancer survivors. © FASEB.