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Effects of strength training on skeletal muscle in rats with cachexia-induced cancer

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Author(s):
Willian das Neves Silva
Total Authors: 1
Document type: Master's Dissertation
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Escola de Educação Física e Esportes (EEFE/BT)
Defense date:
Examining board members:
Antonio Herbert Lancha Junior; Patricia Chakur Brum; Rui Curi
Advisor: Antonio Herbert Lancha Junior
Abstract

The lack of therapies for cachexia is a key problem in cancer treatment. In contrast, resistance exercise training (RET) has been adopted as nonpharmacological anti-catabolic strategy, preventing muscle wasting and muscle dysfunction. However, the role of RET to counteract cancer cachexia is still speculative. Presently, we test whether RET would counteract skeletal muscle wasting in a severe cancer cachexia rat model. Methods: Male Wistar rats were randomly assigned into four experimental groups; 1) untrained control rats injected with saline solution in the bone marrow (control), 2) rats injected with saline solution in the bone marrow and submitted to RET (control + RET), 3) untrained rats injected with Walker 256 tumor cells in the bone marrow (tumor) and 4) rats injected with Walker 256 tumor cells in the bone marrow and submitted to RET (tumor + RET). Skeletal muscle mass and fiber cross sectional area, markers of metabolic and protein turnover impairment, in vivo and ex vivo skeletal muscle function, food intake, tumor growth and mortality rate were assessed. Results: Tumor group displayed skeletal muscle atrophy fifteen days post tumor cells injection as assessed by Plantaris (-20.5%) and EDL (-20.0%) muscle mass. EDL atrophy was confirmed by histological analysis, showing 43.8% decline in the fiber cross sectional area. Even though RET increased the lactate dehydrogenase protein content and fully restored phosphorylated form of 4EBP-1 (i.e. a repressor of mRNA translation) to the control levels in skeletal muscle, it failed to rescue muscle morphology in tumorbearing rats. Indeed, RET has not mitigated loss of muscle function, anorexia, tumor growth or mortality rate. However, loss of strength capacity (assessed by 1-RM test performance) demonstrated a negative correlation with rats´ survival (p = 0.02), suggesting that loss of strength capacity predicts cancer mortality. Conclusions: Bone marrow injection of Walker 256 tumor cells in rats induces cancer cachexia. RET is ineffective to mitigate cancer-induced skeletal muscle wasting in this rat model. However, strength capacity predicts cancer survival, suggesting that new studies are needed to elucidate the putative therapeutic role of different exercise training regimens in counteracting cancer cachexia and tumor progression (AU)

FAPESP's process: 13/04744-4 - Effects of strength training on skeletal muscle in mice with cachexia induced cancer.
Grantee:Willian das Neves Silva
Support Opportunities: Scholarships in Brazil - Master