Journal of Exercise & Organ Cross Talk

Abstract This study aimed to investigate the effects of high-intensity interval training (HIIT) on Adiponectin receptor 1 (AdipR1) gene expression in breast tumor tissue and serum levels of glutathione peroxidase (GPX) and glutathione reductase (GR) in a murine model of breast cancer. Sixteen female BALB/c mice were inoculated subcutaneously with 4T1 murine mammary carcinoma cells (5 × 10⁵ cells/mouse). One week post-inoculation, mice were randomly assigned to either a tumor-bearing control group (Tumor, n=8) or a tumor-bearing group subjected to HIIT (Tumor+HIIT, n=8). The HIIT protocol was performed on a motor-driven treadmill five days/week for four weeks, consisting of six 2-minute high-intensity intervals (18–25 m/min, 80–90% VO₂max) interspersed with 3-minute active recovery periods (5–9 m/min). Twenty-four hours after the final session, tumor tissues were excised for AdipR1 gene expression analysis via quantitative real-time PCR (2^-ΔΔCT method), and serum samples were collected for assessment of GPX and GR levels using ELISA. Statistical comparisons were performed using independent samples t-tests (p<0.05). HIIT significantly upregulated AdipR1 gene expression in breast tumor tissue compared to the control group (p<0.0001). Serum GPX levels were significantly decreased in the Tumor+HIIT group compared to the Tumor control group (p<0.0001). However, no significant difference was observed in serum GR levels between the two groups (p=0.7499). These findings suggest that HIIT may influence breast cancer progression through adiponectin-mediated pathways and oxidative stress regulation, providing a potential non-pharmacological adjunctive strategy for breast cancer management. Further studies are warranted to elucidate the underlying molecular mechanisms and clinical implications.

Abstract This study investigated the effects of high intensity interval training (HIIT), Nano-selenium supplementation, and their combination on the expression of LDHA, LDHB, and the LDHA/LDHB ratio in mice breast tumor tissue. Female mice (n=32) were inoculated with mammary adenocarcinoma cells (4T1) and randomly assigned to four groups (n=8 each): tumor control (Tu), tumor+HIIT (Tu+Ex), tumor + Nano-selenium (Tu+Nsel, 2 mg/kg/day orally), and tumor+HIIT+Nano-selenium (Tu+Ex+Nsel). HIIT was performed on a treadmill (30 min/day, 5 days/week) for four weeks. One-way ANOVA revealed significant differences among groups for LDHA expression (F=38.66, p<0.0001). Compared to the Tu group, all intervention groups (Tu+Ex,Tu+Nsel, and Tu+Ex+Nsel) showed a significant increase in LDHA expression (p<0.05). The greatest increase was observed in the combined treatment group (Tu+Ex+Nsel), which was significantly higher than both Tu+Ex and Tu+Nsel (p<0.001). For the LDHA/LDHB ratio, a significant overall effect was found (F=163.87, p<0.0001). The Tu+Nsel group exhibited a significant increase in the ratio compared to the Tu group (p<0.05), whereas both Tu+Ex and Tu+Ex+Nsel showed a significant decrease in the ratio (p<0.05). The ratio in the Tu+Nsel group was also significantly higher than in the two exercise containing groups (p<0.05). HIIT and Nano-selenium independently upregulate LDHA expression in breast tumor tissue, with an additive effect when combined. However, only Nano-selenium alone increased the LDHA/LDHB ratio, while exercise-based interventions (with or without Nano-selenium) decreased this ratio. These findings suggest that exercise and Nano-selenium differentially shift the balance between LDHA and LDHB, potentially influencing tumor lactate metabolism and the tumor microenvironment.

Abstract Cancer is the leading cause of death worldwide, with breast cancer posing a high risk for women. Immunotherapy has shown efficacy, and exercise is recognized for its role in cancer management. Combining both may enhance therapeutic outcomes. This study examined 30 female BALB/c mice (average weight: 17.76g), divided into five groups (n=6 each). After treadmill acclimation, they underwent two 6-week training protocols and a 4-week protocol post-cancer induction. Data analysis was performed using one-way ANOVA. The findings revealed significant differences in body weight among the EIEA and EIA groups compared to the control group. Similarly, in the heart weight analysis, both EIEA and EIA groups showed significant differences compared to the control (p<0.05). Notably, the combination of exercise and anti-PD-L1 antibody treatment effectively prevented weight loss in both body mass and heart weight. This protective effect may be attributed to the mitigation of cachexia, a common complication in cancer that leads to severe weight loss and muscle wasting. These results suggest that integrating physical activity with immunotherapy could serve as a potential strategy to counteract cancer-induced weight deterioration.

Abstract Physical activity performance of patients during and after breast cancer treatment is common and is associated with increased toxicity from treatment, shorter time to tumor progression, and decreased survival. Exercise is a potential intervention to maintain or increase physical performance. We conducted a meta-analysis review of the 1-year tailored exercise training, according to cytokine levels and immune function with emphasis on IL-6 in breast cancer patients. A comprehensive search was performed in September 2022 for randomized controlled trials reporting the effects of structured exercise training on breast cancer effect with cytokine levels and immune function with an emphasis on IL-6 during or after cancer treatment. A random-effects meta-analysis was completed using the absolute net difference in the change between intervention and control groups as the outcome measure. Sensitivity and subgroup analyses were also performed. Data from 18 studies involving 1833 breast cancer survivors were included in the meta-analysis. Overall, there was a significant benefit of exercise training compared with the control (I2 = 71.3%, 95% CI = 38.4% to 77.6%, P < 0.001). Subgroup analysis showed positive effects for resistance training and aerobic training and for exercise training conducted during or after cancer treatment. Compared with usual care, exercise training has a beneficial effect on in women with breast cancer, both during and after cancer treatment. Given the physiological and functional importance of women with breast cancer, oncologists should encourage their patients to engage in regular exercise training, with particular emphasis on resistance training.

Abstract The modifications of PGC-1𝛼 induce the change of the carcinogenesis and tumor growth and lead to increased antioxidant enzymes. The present study aimed to determine the cross talk between PGC1-α mRNA expression, tumor volume growth, and total antioxidant capacity in breast cancer model mice, followed by discontinuous aerobic exercise and vitamin D. In the present study, 40 female NMRI mice were randomly assigned into five equal groups (n=8): healthy control group (H.C), cancer control group (Ca.C), cancer with the vitamin D group (U.Ca.VD), cancer exercise training group (Ca. Ex), and cancer exercise training with the vitamin D group (Ca.Ex.VD). As the results indicate, the bodyweight of cancer groups (p=0.041, F=3.61) and the tumor growth rate significantly reduced compared to the H.C group. The results indicated that the PGC-1α mRNA expression and TAC (p=0.013, F=5.16) change significantly different between the study groups. Besides, based on the results, a significant positive correlation was observed between PGC1-α and tumor volume growth among the groups, whereas a negative relationship exists between PGC1-α and TAC and among TAC and tumor volume growth only in the Ca. Ex.VD group. The correlation between the variables confirms using vitamin D treatment with the implementation of discontinuous aerobic exercise, as a synergistic effect, improves the total antioxidant capacity and is effective in controlling tumor growth. We recommend that further studies be done on exercise training along with supplementation intake synergistic.