Combined High-Intensity Interval Training and Nano-Selenium Modulate GLUT۴, AMPK, and AKT Gene Expression in a Murine Breast Cancer Model

Background: This study investigated the effects of high-intensity interval training (HIIT), nano-selenium (NS), and their combination on the expression of key metabolic genes (GLUT۴, AMPK, and AKT) in breast tumor tissue of a murine model. Methods: Thirty-two male BALB/c mice bearing ۴T۱ mammary tumors were randomly assigned to four groups (n = ۸ each): tumor-bearing control (BT), tumor +HIIT (BT+EX), tumor + nano-selenium (BT+ NS), and tumor + HIIT + nano-selenium (BT+EX+NS). HIIT was performed on a treadmill for ۳۰ minutes/day, five days/week over four weeks. Nano-selenium (۰.۵ mg/kg) was administered daily by oral gavage. Real-time PCR was used to quantify GLUT۴, AMPK, and AKT mRNA expression in tumor tissues. Results: Both HIIT and nano-selenium significantly reduced GLUT۴ expression compared to controls (p<۰.۰۰۰۱), with no significant difference between them (p=۰.۹۹۱۲). The combination therapy produced the greatest reduction (p<۰.۰۰۰۱ vs. either monotherapy). For AMPK, all treatments significantly increased expression relative to controls (p<۰.۰۰۰۱), with the combination showing the highest upregulation (p<۰.۰۰۰۱ vs. BT+ EX and BT+NS). AKT expression was significantly decreased by all interventions (p<۰.۰۰۱ to p< ۰.۰۰۰۱), and the combination was more effective than either treatment alone (p<۰.۰۱ and p<۰.۰۰۰۱, respectively). No significant differences between BT+ EX and BT+NS were observed for GLUT۴ (p=۰.۹۹۱۲) or AKT (p=۰.۱۲۷۶), but AMPK was higher in the BT+NS group compared to BT+ EX (p=۰.۰۴۴۵). Conclusion: HIIT and nano-selenium independently and synergistically downregulate GLUT۴ and AKT while upregulating AMPK in breast tumor tissue. The combination of exercise and nano-selenium appears to exert a more potent modulation of glucose metabolism-related genes than either intervention alone, suggesting a potential adjuvant strategy for breast cancer management.

کلیدواژه ها:

Breast cancer ، High-intensity interval training ، Nano-selenium ، GLUT۴ ، AMPK ، AKT ، Gene expression