Scholarship 22/11891-2 - Exercício físico, Heme oxigenase-1 - BV FAPESP
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EFFECT OF AEROBIC TRAINING ON B-ADRENERGIC SIGNALING AND ITS RELATIONSHIP WITH HEME OXYGENASE-1 IN THE TUMOR MICROENVIRONMENT

Grant number: 22/11891-2
Support Opportunities:Scholarships in Brazil - Doctorate
Start date until: December 01, 2022
End date until: November 30, 2025
Field of knowledge:Health Sciences - Physical Education
Principal Investigator:Patricia Chakur Brum
Grantee:Matheus da Silveira Costa
Host Institution: Escola de Educação Física e Esporte (EEFE). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The effects of the hyperactivity of adrenergic pathway in different stages of cancer have been investigated both in vitro and in vivo. Stimulation of the BAR pathway increases proliferation, migration, viability and invasion of tumor cells. In addition, exposure to stressors, both in animal models and in clinical studies, showed increased incidence and disease progression in different types of cancer. On the other hand, strategies that attenuate BAR activation led to a suppressive effect on pro tumoral parameters in some types of cancer. Interestingly, BAR signaling also regulates a protein called hemeoxygenase-1 (HO-1), which provides antioxidant and anti-inflammatory protection, which may be desirable in healthy tissues, but also contributes to tumor proliferation in the microenvironment and disease progression. Indeed, cell culture studies showed that high levels of HO-1 in the tumor environment result in increased cell proliferation, migration and invasion. In an animal model, induced increase in HO-1 leads to tumor growth and, in fact, samples of human colorectal tumors show high levels of HO-1. Additionally, exercise training has been considered a complementary therapy to cancer and one of its known effects is on the attenuation of sympathetic hyperactivity in several chronic diseases. In the present study, we will test the hypothesis that stimulation of BAR receptors will induce increases in proliferation, migration, viability and invasion in murine colon carcinoma cells (CT26) and that HO-1 will play an important role in this answer. In a second step, we will test whether exercise training associated with the modulation BAR is able to reduce tumor growth leading to a down regulation in BAR signaling and reduced activity of HO-1 in mice with CT26 colon cancer cells.

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