Journal of Practical Studies of Biosciences in Sport

Journal of Practical Studies of Biosciences in Sport

Comparison of the effects of selected resistance training with and without resveratrol supplementation on insulin-like growth factor-1, malondialdehyde, and total antioxidant capacity in mice with breast cancer

Document Type : Original Article

Authors
Azadeh Taheri 1
Jamshid Benaei Borogeni 2
Hamid zahdi 2
Saeed Keshavarz 2
1 PhD Student in Department of Sport Sciences, Na.C., Islamic Azad University, NajafAbad, Iran
2 Department of Sport Sciences, Na.C., Islamic Azad University, NajafAbad, Iran.
10.22077/jpsbs.2026.11318.2044
Abstract
Extended Abstract
Background and Aim: Breast cancer progression is associated with dysregulated cellular signaling and impaired redox homeostasis. Activation of the insulin-like growth factor-1 (IGF-1) axis may promote tumor-cell proliferation and survival, whereas excessive production of reactive oxygen species (ROS) can contribute to lipid peroxidation and oxidative damage. Malondialdehyde (MDA) is commonly used as a marker of lipid peroxidation, while total antioxidant capacity (TAC) reflects the overall antioxidant capacity of biological systems. Resistance training (RT) may induce metabolic and antioxidant adaptations that influence oxidative balance and tumor-related processes. Resveratrol (RSV), a naturally occurring polyphenol, has also been reported to exert antioxidant effects and modulate cellular signaling pathways. However, evidence regarding the independent and interactive effects of RT and RSV in experimental breast cancer remains limited. Therefore, this study aimed to investigate the independent and interactive effects of RT and RSV supplementation on IGF-1 gene expression, MDA levels, and TAC in mice with breast cancer.
Materials and Methods: This laboratory study employed a posttest-only controlled design. Fifty female BALB/c mice, aged 8–10 weeks and weighing 20–25 g, were housed under standard laboratory conditions with a temperature of 20–24 °C, relative humidity of 50%–60%, and a 12:12-h light–dark cycle. Following a one-week acclimatization period, breast cancer was induced in the cancer-bearing groups by injecting 5 × 106 4T1 murine breast cancer cells suspended in 100 μL of phosphate-buffered saline into the mammary fat pad. Tumor development was monitored daily, and the interventions commenced once tumors became palpable.
The mice were randomly allocated to five groups (n=10 per group): healthy control (HC), cancer control (CC), resistance training (RT), resveratrol supplementation (RSV), and combined resistance training plus resveratrol supplementation (RT+RSV). The Resistance training protocol consisted of climbing a 1.1-m ladder inclined at 80°, with a load attached to the tail. Training was performed three times per week for eight weeks. Each session included four to eight climbs, separated by one-minute recovery intervals. The training load was progressively increased from approximately 50% of maximal carrying capacity (MCC) at the beginning of the intervention to 100% by the end. MCC was reassessed periodically to adjust training intensity.
Resveratrol was administered orally by gavage to the supplemented groups at a dose of 25 mg/kg body weight/day for eight weeks. At the end of the intervention period, the animals were anesthetized with ketamine and xylazine and subsequently euthanized. Tumor tissues were excised, washed with an ice-cold solution, and stored at −80 °C until analysis. Total RNA was extracted, complementary DNA was synthesized, and relative IGF-1 gene expression was quantified by RT-qPCR using the 2−ΔΔCt method. Tumor-tissue MDA levels and TAC were measured using colorimetric assays. Data were analyzed using SPSS version 27. One-way ANOVA followed by Tukey’s post hoc test and two-way ANOVA were used as appropriate. Statistical significance was set at p<0.05 for all analyses, and results were interpreted accordingly.
Findings: Compared with HC, the CC group exhibited higher IGF-1 gene expression and MDA levels, along with lower TAC . The Mean IGF-1 fold-change values were 1.00±0.30 in HC, 1.50±0.15 in CC, 1.30±0.12 in RT, 1.20±0.10 in RSV, and 1.05±0.08 in RT+RSV. Corresponding IGF-1 log₂ fold-change values were 0.30±0.14, 0.58±0.14, 0.38±0.13, 0.26±0.12, and 0.11±0.07, respectively. Thus, IGF-1 expression was highest in CC, whereas the combined intervention reduced it to a value close to HC.
MDA levels were 2.50±0.40 in HC, 4.60±0.70 in CC, 3.70±0.60 in RT, 3.40±0.80 in RSV, and 2.90±0.50 in RT+RSV. Compared with CC, MDA decreased by 22.2% in RT, 28.9% in RSV, and 40.0% in RT+RSV. TAC values were 1.20±0.08 in HC, 0.80±0.07 in CC, 1.05±0.09 in RT, 1.10±0.10 in RSV, and 1.18±0.09 in RT+RSV. Relative to CC, TAC increased by 31.3% following RT, 37.5% following RSV, and 47.5% following the combined intervention. Overall, both interventions were associated with improvements in the measured oxidative-status indicators, with the greatest numerical improvements observed in the RT+RSV group.
Two-way ANOVA of the four cancer-bearing groups revealed significant main effects of RT and RSV on all variables. For IGF-1, the main effects of RT (F=34.61, p<0.001) and RSV (F=70.16, p<0.001) were significant, whereas their interaction was not (F=2.20, p=0.14). For MDA, the main effects of RT (F=37.92, p<0.001) and RSV (F=68.92, p<0.001) were significant, but their interaction was not (F=3.28, p=0.07). For TAC, the main effects of RT (F=25.41, p<0.001) and RSV (F=59.63, p<0.001), as well as their interaction (F=19.20, p<0.001), were significant (Figure 1).
As shown in Figure 1, the combined intervention brought MDA and TAC values closer to those observed in the healthy control group. The significant interaction for TAC, but not for MDA or IGF-1, suggests a specific potentiating effect of the combined intervention on overall antioxidant defense. Changes in IGF-1 and MDA primarily reflected the independent effects of RT and RSV.
Conclusion: Eight weeks of RT and RSV supplementation independently reduced IGF-1 gene expression and MDA levels while increasing TAC in mice bearing 4T1 breast tumors. The combined RT+RSV intervention produced the most favorable response, with the lowest IGF-1 and MDA levels and the highest TAC among cancer-bearing groups. However, a statistically significant interaction between RT and RSV was detected only for TAC. Therefore, the greater improvement in TAC may indicate a potentiating effect of the combined intervention on antioxidant defense, whereas changes in IGF-1 and MDA mainly reflect the independent effects of RT and RSV. These findings provide preclinical evidence that combining RT with RSV supplementation may improve redox balance and modulate biological factors associated with breast cancer progression. Nevertheless, because this study used an animal model and did not assess tumor size, histopathology, or clinical outcomes, the findings should not be generalized to patients. Further mechanistic and controlled clinical studies are warranted.
Compliance with Ethical Guidelines: All animal procedures were conducted in accordance with accepted ethical principles and institutional guidelines for the care and use of laboratory animals. The study protocol was reviewed and approved by the relevant institutional ethics committee.
Funding: This research received no specific grant or financial support from any public, commercial, or non-profit funding organization and was conducted using the researchers’ own resources.
Conflicts of Interest: The authors declare that they have no financial or non-financial conflicts of interest related to this study.
Keywords
Breast cancer
Resistance training
Resveratrol supplementation
Growth biomarkers
Oxidative status
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Journal of Practical Studies of Biosciences in Sport
Volume 14, Issue 39
Summer 2026
Pages 130-145