Synergistic Effect of Endurance Training Combined with Curcumin on Intratumoral Expression of Interleukin-4 (Il4) and Stat-6 in Female Mice with Breast Cancer

Abstract

Introduction: The Il4/Stat-6 signaling axis is one of the most important pathways involved in the growth and development of breast cancer. Hence, the aim of the present study was to investigate the synergistic effect of endurance training along with curcumin on the intratumoral expression of Il4 and Stat-6 in female BALB/c mice with breast cancer. Methods: Forty BALB/c mice (4-5 weeks old) were randomly divided into four groups including exercise, curcumin, exercise-curcumin, and control. The 4T1 breast Tumors were transplanted subcutaneously in the right flank of all mice. Then, endurance training (5 days per week) was performed, and curcumin (6 times per week) was given by gavage for five weeks. The intratumoral expression of Il4 and Stat-6 were measured using the qRT-PCR method. One-way analysis of variance followed by LSD post hoc test, was used for the statistical analysis. P< 0.05 was considered statistically significant. Results: A significant decline in tumor growth was observed in all intervention groups compared with the control group (P<0.05). Endurance training with curcumin resulted in a significant reduction in the intratumoral expression of Il4 and Stat-6 in comparison with the control group (P=0.001 for both genes). Significant reductions in the expression of Il4 (P=0.019) and Stat-6 (P=0.001) were also observed in the endurance exercise group. Curcumin only reduced Stat-6 gene expression compared with the control group (P=0. 001). Conclusion: Five weeks of endurance training with curcumin seems to be more effective in treatment of cancer compared with either of these non-pharmacological strategies alone.

Exercise protocols: The gap between preclinical and clinical exercise oncology studies

“…Human and animal exercise activate a myriad of cellular pathways which contribute to remodeling and/or adaptation [ [8] , [9] , [10] , [11] , 13 ]; however, the extent to which given pathways yields anticancer benefits, and whether this is of the similar significance in animal and humans, is unclear. Nevertheless there is evidence of preclinical-clinical commonalit; for example, high intensity interval training appears to evoke similar potent benefits [ [19] , [20] , [21] , [22] , [23] ]. Understanding the exercise tolerance thresholds (especially clinically) together with exercise stimulus thresholds (to elicit a meaningful beneficial physiological response) will combine to establish suitable exercise protocols oncology studies.…”

“…This Other preclinical studies have used a similar VO2-based frameworks [ [20] , [21] , [22] , [23] ]. Similar protocols were also used in diabetic [ 57 , 58 ] and also fatty liver animals [ 12 ], aiming to generate information with a higher probability of translation to clinical studies.…”