Effect of aerobic physical training associated with chemotherapy with doxorubicin in mice with Lewis Lung Carcinoma (LLC): role of treatments in skeletal striated muscle and tumor

• Grant number: 18/17631-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2018
• End date: October 31, 2019
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: José Cesar Rosa Neto
• Grantee: Rafael Bissi Ricci de Barros
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cancer is the second most deadly disease in the world. Most of the treatments against this morbidity involve the use of chemotherapy, but despite the antiproliferative effects of this therapy, the toxicity is very great, leading to a decrease in the expectation and quality of life. The association of tumor to therapy often induces proteolysis, leading to decreased ability of the individual to perform daily tasks. Physical training may be an important adjuvant therapy in reducing the side effects of chemotherapy, postulating that some of these effects are disseminated by the production and release of myocytes, which have a potential anti-inflammatory effect capable of neutralizing the chronic inflammation caused by the tumor. To investigate these effects, we will cycle with 4 doses of doxorubicin (2.5 mg/kg body weight) every 72 hours for two weeks. Chemotherapy will begin one week after the inoculation of LLC tumor cells into female C57BL6 mice, and physical training will occur within two weeks, concurrent with chemotherapy. We will evaluate the inflammatory response through the ELISA assay with the cytokines TNF-±, IL-10, IL-6, IL-1², muscle and tumor, immunohistochemistry for proliferation and cell depletion markers, and the protein degradation pathway ubiquitins ligases by RT-PCR. We will perform morphological analysis with Hematoxylin - Eosin staining to measure and compare the size of the fibers.