Endurance Training Attenuates Angiogenesis Following Breast Cancer by Regulation of MiR-126 and MiR-296 in Breast Cancer Bearing Mice

Abstract

Background: In recent decades, various studies have shown a relationship between exercise and decreased mortality in patients with breast cancer. However, potentially involved molecular mechanisms are yet to be detected. Objectives: The goal of this study was to investigate the effect of endurance training on gene expression of miR-126, miR-296, HGS and protein expression of VEGF-A, in the tumor tissues of breast cancer bearing mice. Methods: Twelve laboratory female BALB/c mice, weighing 19 ± 1.05 g, were randomly divided into two groups of 6 each; that is, endurance training and control, after inducing cancer by subcutaneous injection with MC4-L2 into their right sides. Each session of endurance training involves 60-min of running on a treadmill at an intensity of 60% - 65% VO2max, five days a week for 10 weeks. Twenty-four hours after the last exercise session, the mice are sacrificed and the genes expression is measured. Results: Endurance training caused a significant decrease in miR-296 (P < 0.05) and an increase in the HGS (P < 0.05) and miR-126 (P < 0.05) at mRNA level, and a decrease in VEGF-A (P < 0.05) at protein level in tumor tissue compared to the controls. Decrease in proangiogenic factors and induction of anti-angiogenic factors are associated with decreased growth of tumor volume (P < 0.05) in the endurance training group compared to the control group. Conclusions: Data from this study demonstrate that endurance training can significantly decreases tumor growth in BALB/c mice. Endurance training mediates its effects through reduction of level of the vascular endothelial growth factors (VEGF) and VEGF receptors (VEGFR) in tumor tissue.