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EXERCISE PRIOR TO TUMOR-BEARING PROTECTS CARDIAC FUNCTION AND INHIBITS TUMOR GROWTH IN FEMALE TUMOR-BEARING MICE

L Tichy
TL Parry

Abstract

Louisa Tichy, Traci L. Parry. University of North Carolina at Greensboro, Greensboro, NC.

Background: Cancer cachexia, a metabolic wasting syndrome, leads to death in up to 20% of cancer patients. There are no clear diagnostic criteria and cancer cachexia remains an untreated condition. Aerobic exercise has been shown to slow the development of cachexia and attenuate cachexia-mediated muscle loss. However, the most effective timing, intensity, and duration of exercise as a protective and preventative measure against cancer cachexia remains unknown. Therefore, the purpose of this study was to examine the effects and underlying pathways of preconditioning exercise as a protective measure for tumor-mediated muscle wasting. Methods: Female LC3 Tg+ and WT 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 treadmill exercise protocol (TM) or remained sedentary (SED). Next, T groups were implanted with tumor cells (5x105 LLC cells in flank) while NT groups remained non-tumor for additional 4 weeks. To examine effects of exercise on tumor growth and muscle wasting, grip strength, echocardiography, and tumor evaluations were taken at baseline, 8-week, and 12-week time points. After the 12-week study, muscle and tumor tissue was collected and weighed. Results: Tumor bearing resulted in significant decline in cardiac function. SED+T showed significant decrease in fractional shortening (P<0.05). Interestingly, preconditioning exercise (prior to tumor bearing) appeared to preserve cardiac function (TM+T not significantly different than SED+NT). Exercise-mediated cardioprotection coincided with lower TGF-β and p62 protein expression and downregulated early-phase autophagy in TM+T mice compared to SED+T mice. Additionally, TM resulted in a 20-fold decrease in estimated tumor volume (P<0.05) and a 60% decrease in tumor mass (P<0.05) compared to SED tumors. Conclusion: These data indicate cardioprotective and tumor suppressive effects of preconditioning exercise by preserving cardiac function, regulating autophagic pathways, and stunting tumor growth. These findings are crucial in identifying the significance of exercise, specifically the timing of exercise, as a protective and preventative measure against the detrimental effects of cancer cachexia.

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