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 Opportunities: Scholarships in Brazil - Doctorate
• Start date: March 01, 2016
• End date: October 31, 2020
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: José Cesar Rosa Neto
• Grantee: Edson Alves de Lima Junior
• Host 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

Abstract

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.

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)

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, JUL 2019. (15/26148-0, 15/17068-2, 16/16712-8)

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, NOV 2020. (15/17068-2, 13/09367-4, 19/01244-7, 19/09854-9)

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, DEC 2018. (13/09367-4, 15/17068-2)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

LIMA JUNIOR, Edson Alves de. Response to treatment with metformin and endurance exercise in mitigating muscle disorders induced by doxorubicin therapy.. 2020. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.