Abstract
Triple-negative breast cancer (TNBC) stands out for its aggressiveness and accelerated rate of proliferation. Evidence shows that exercise may exert antitumorigenic effects, but the biochemical mechanisms underlying them remain unclear. Our objective was to evaluate the ability of exercise to modulate tumor growth and energy metabolism in an experimental TNBC model. Female BALB/c mice were sedentary or trained for 12 weeks and inoculated with 1 × 104 4T1 cells in the eighth week. Analyzes of macronutrient oxidation, mitochondrial respiration, and expression of genes related to cell metabolism were performed. The results showed that the trained group had a smaller tumor mass and the mitochondria in the tumors presented lower respiratory rates in the state of maximum electron transport capacity. Additionally, the tumors of the exercised group showed a higher expression of genes related to tumor suppressors, while the genes linked with cellular growth were similar between groups. Furthermore, the training modulated the corporal macronutrient oxidation to almost exclusive carbohydrate oxidation, while the sedentary condition metabolized both carbohydrate and lipids. Therefore, the exercise reduced tumor growth, with an impact on mitochondrial and macronutrient metabolism. Our results shed light on the understanding of the antitumorigenic effects of physical exercise, particularly regarding the metabolic transformations in TNBC.
Highlights
Breast cancer ranks first among all cancers and the estimated incidence in 2018 was over two million new cases globally [1]
Voluntary physical exercise has been shown to reduce tumor growth rate after mice were inoculated with 5 × 104 [22]
Moderate physical exercise on the treadmill was not able to affect Triple-negative breast cancer (TNBC) tumor growth in mice inoculated with 1 × 106 4T1 cells [34]
Summary
Breast cancer ranks first among all cancers and the estimated incidence in 2018 was over two million new cases globally [1]. Triple-negative breast cancer (TNBC) represents 15%–20% of all breast cancers [2,3], and is characterized by an accelerated rate of proliferation, large tumor size, and highest risk of distant metastases [4]. These characteristics contribute to the poor prognosis and overall reduction in survival of patients with TNBC compared to other subtypes of breast cancer [3,4]. Despite breast cancer being a heterogeneous disease at the molecular level [5], some mutations are often found, for example, an increase in gene expression of the PTEN-Akt-mTOR pathway, linked to growth and cellular proliferation [5,6].
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