Exercise Reduces the Resumption of Tumor Growth and Proteolytic Pathways in the Skeletal Muscle of Mice Following Chemotherapy

• Published in: Cancers Vol. 12; no. 11; p. 3466
• Main Authors: Alves de Lima, Edson, Teixeira, Alexandre Abilio de Souza, Biondo, Luana Amorim, Diniz, Tiego Aparecido, Silveira, Loreana Sanches, Coletti, Dario, Busquets Rius, Silvia, Rosa Neto, José Cesar
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 20.11.2020; MDPI
• Subjects: Atrophy; Cachexia; Cancer; Cancer therapies; Chemotherapy; Doxorubicin; Exercise; Fitness equipment; Forkhead protein; Gastrocnemius muscle; Gene expression; Growth rate; Health aspects; Lung carcinoma; Medical prognosis; Mortality; Muscles; Musculoskeletal system; Myostatin; Patient outcomes; Physical fitness; Proteolysis; Skeletal muscle; Toxicity; United States
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers12113466

The pathogenesis of muscle atrophy plays a central role in cancer cachexia, and chemotherapy contributes to this condition. Therefore, the present study aimed to evaluate the effects of endurance exercise on time-dependent muscle atrophy caused by doxorubicin. For this, C57 BL/6 mice were subcutaneously inoculated with Lewis lung carcinoma cells (LLC group). One week after the tumor establishment, a group of these animals initiated the doxorubicin chemotherapy alone (LLC + DOX group) or combined with endurance exercise (LLC + DOX + EXER group). One group of animals was euthanized after the chemotherapy cycle, whereas the remaining animals were euthanized one week after the last administration of doxorubicin. The practice of exercise combined with chemotherapy showed beneficial effects such as a decrease in tumor growth rate after chemotherapy interruption and amelioration of premature death due to doxorubicin toxicity. Moreover, the protein degradation levels in mice undergoing exercise returned to basal levels after chemotherapy; in contrast, the mice treated with doxorubicin alone experienced an increase in the mRNA expression levels of the proteolytic pathways in gastrocnemius muscle (Trim63, Fbxo32, Myostatin, FoxO). Collectively, our results suggest that endurance exercise could be utilized during and after chemotherapy for mitigating muscle atrophy promoted by doxorubicin and avoid the resumption of tumor growth.