Exercise Counteracts Inflammation And Muscle Proteolysis Mediators In Tumor-bearing Mice

Cancer cachexia is characterized by unexplained weight loss accompanied by muscle atrophy, which may result from abnormal increases in inflammation and E3 ubiquitin ligases. While the benefits of exercise countermeasures (EC) for enhancing muscle mass are well recognized, their potential to combat muscle loss and downregulate inflammatory and proteolysis mediators remains to be elucidated. PURPOSE: To determine the clinical efficacy of different types of EC on alterations in muscle wet weight and inflammatory mediators and E3 ubiquitin ligases in ApcMin/+ mice, a model of intestinal neoplasia. METHODS: Forty ApcMin/+ mice were randomly assigned to sedentary control (SC-Apc n = 10), aerobic exercise (A-Apc n = 10), resistance exercise (R-Apc n = 10), and combination of aerobic and resistance exercise (AR-Apc n = 10) for an 8-wk intervention period. Additionally, ten wild-type C57BL mice (WT) served as a control group. The A-Apc group performed treadmill running at a speed of 18 m/min for 55 min at a 5% grade. The R-Apc group performed 3 sets of 4 repetition ladder climbs with weight attached to the base of their tail. The AR-Apc group performed the combined aerobic and strength program. Gastrocnemius wet weight and mRNA levels of inflammatory mediators [Tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6)] and E3 ubiquitin ligases (atrogin-1) were assessed at post-intervention. Statistical analyses were conducted using one-way ANOVA. RESULTS: Following the 8-wk intervention, the gastrocnemius wet weight of A-APC was 17.1% higher than SC-APC, which approached statistical significance (p = 0.076). TNF-α mRNA expression in SC-APC was significantly greater than WT (+145 ± 59%, p = 0.024) and was non-significantly higher than AR-APC (+123 ± 54%, p = 0.085). SC-APC presented greater IL-6 mRNA levels compared to WT (+191 ± 71%, p = 0.024), with a non-significant higher level than AR-APC (+116 ± 45%, p = 0.092). Atrogin-1 mRNA expression in SC-APC was greatly higher compared to WT (+634 ± 106%, p < 0.001) and AR-APC (+137 ± 89%, p = 0.021). CONCLUSION: Our findings indicate that aerobic exercise may help mitigate muscle wasting, while combined exercise appears to attenuate proteolysis mediators in tumor-bearing mice, suggesting EC as a promising therapeutic strategy to counteract catabolic syndrome in cancer patients. Supported by: Supported by U54 Partnership for The Advancement of Cancer Research (PACR) Grant.