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Effect of aerobic exercise training associated with doxorubicin chemotherapy in mice with Lewis lung carcinoma (LLC). Role of adiponectin in skeletal muscle and tumor.

Grant number: 15/17068-2
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): March 01, 2016
Effective date (End): October 31, 2020
Field of knowledge:Biological Sciences - Biochemistry - Metabolism and Bioenergetics
Principal researcher:José Cesar Rosa Neto
Grantee:Edson Alves de Lima Junior
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated scholarship(s):19/01244-7 - Pharmacological and non-pharmacological management of muscle wasting, BE.EP.DR


Cancer is currently considered a leading cause of mortality and morbidity in the world. For the treatment of this disease with frequency pharmacological strategies are used. Doxorubicin is a widely used chemotherapy in the clinical practice. However, its application is limited by their side effects as observed in skeletal muscle and adipose tissue. Adiponectin, in turn, is an adipokine mainly produced by white adipose tissue and establishing cross-link between various organs. It has anti-diabetogenic action in skeletal muscle and anti-proliferative action on tumor cells. Since exercise is a potential co-adjuvant treatment to chemotherapy and cancer the objective of this project is to investigate the effects of physical exercise associated to chemotherapy with doxorubicin in mice with Lewis lung carcinoma (LLC) are dependent on adiponectin in skeletal muscle and in the tumors. For that animals will be used C57BL / 6 and adiponectin knockout animals (Adipo KO). The animals will be treated with doxorubicin (5 mg / kg intraperitoneally), moderate aerobic exercise (60% level. Max) or both. The following groups will be used: control (CT group), LLC (tumor group), LLC + DOX (doxorubicin + tumor group), LLC + T (+ tumor group training) and LLC + DOX + T (tumor group + doxorubicin + training ). Additionally we use animal groups Adipo KO to evaluate the effects of training and chemotherapy are dependent on doxorubicin. Survival, physical performance and tumor size is evaluated. In skeletal muscle will hold the gene and protein expression Involved in insulin signaling, glucose uptake and oxidation of lipids. Immunohistochemistry, we characterize the phenotype of muscle fibers. The tumor will perform protein expression Involved in IGF-1-AKT-mTOR-p53 signaling. In vitro assays using autologous serum trained animals will be used to assess cell proliferation and apoptosis.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ALVES DE LIMA, JR., EDSON; TEIXEIRA, ALEXANDRE ABILIO DE SOUZA; BIONDO, LUANA AMORIM; DINIZ, TIEGO APARECIDO; SILVEIRA, LOREANA SANCHES; COLETTI, DARIO; BUSQUETS RIUS, SILVIA; ROSA NETO, JOSE CESAR. Exercise Reduces the Resumption of Tumor Growth and Proteolytic Pathways in the Skeletal Muscle of Mice Following Chemotherapy. CANCERS, v. 12, n. 11, . (15/17068-2, 13/09367-4, 19/01244-7, 19/09854-9)
CABRAL-SANTOS, CAROLINA; DE LIMA JUNIOR, EDSON ALVES; DA CRUZ FERNANDES, ISABELA MAIA; PINTO, RAFAEL ZAMBELLI; ROSA-NETO, JOSE CESAR; BISHOP, NICOLETTE CHARLLOTE; LIRA, FABIO SANTOS. Interleukin-10 responses from acute exercise in healthy subjects: A systematic review. Journal of Cellular Physiology, v. 234, n. 7, p. 9956-9965, . (15/17068-2, 16/16712-8, 15/26148-0)
DE LIMA, JR., EDSON A.; DE SOUSA, LUIS G. O.; TEIXEIRA, ALEXANDRE ABILIO DE S.; MARSHALL, ANDREA G.; ZANCHI, NELO E.; ROSA NETO, JOSE C.. Aerobic exercise, but not metformin, prevents reduction of muscular performance by AMPk activation in mice on doxorubicin chemotherapy. Journal of Cellular Physiology, v. 233, n. 12, p. 9652-9662, . (13/09367-4, 15/17068-2)

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