Exercise Preconditioning Preserves Skeletal Muscle Function and Stunts Tumor Growth in Male Mice

Abstract

BACKGROUND Cancer cachexia is a complex muscle and fat wasting disorder that results in death in up to one-third of cancer patients. Currently, there are no clear diagnostic criteria, its effects are irreversible, and it cannot be treated. Therefore, a great need exists to better understand this disease. Research has shown that exercise has a positive impact on preserving muscle mass and inhibiting tumor growth, but questions remain regarding the timing, safety, and underlying mechanisms of benefits of exercise in cancer survivors. Therefore, the purpose of this study was to examine the effects of preconditioning exercise as a protective measure for cancer cachexia. METHODS To examine the effects of preconditioning exercise on skeletal muscle wasting and tumor growth, male LC3 Tg+ and sibling matched wildtype mice were randomly separated into four groups: sedentary non-tumor bearing (SED+NT), sedentary tumor bearing (SED+T), exercise non-tumor bearing (TM+NT), and exercise tumor bearing (TM+T). Mice underwent either 8 weeks of progressive treadmill trained exercise (TM) or remained sedentary. This was followed by 4-week sedentary period of tumor bearing (1x105 LLC cells in flank) or non-tumor bearing (NT). Grip strength, muscle mass, and tumor growth characteristics were measured to examine the protective effects of exercise in cancer cachexia skeletal muscle wasting. RESULTS Tumor bearing led to significant declines in muscle strength. Both SED+T and TM+T showed a significantly lower grip strength compared to non-tumor bearing groups (P <0.05). More importantly, the TM+T group showed a significant improvement (preservation) in grip strength versus the SED+T group (p<0.05), which were the weakest of all groups. In step with this finding, SED+T exhibited significantly smaller gastrocnemius muscle mass compared to TM+T (P<0.05). When comparing tumor characteristics, TM+T exhibited 2-fold smaller tumor mass (P<0.05) and 16-fold smaller tumor volume (P<0.001) compared to SED+T tumors. CONCLUSION These data indicate that preconditioning exercise is capable of eliciting a protective effect against cancer cachexia-mediated declines in muscle function and mass. This may be related to the massive stunt in tumor growth that was associated with exercise preconditioning, indicating that the protective effects of exercise may last for a period even when exercise is ceased. Such data are critical in understanding the importance of exercise in cancer cachexia and how the timing of exercise (preconditioning) can play a major role in protecting survivors against the effects of cachexia.