1 Investigating the Effect of 12-Week Swim Training and Vitamin C Supplementation on TGF-β Expression in Lung Tissue of Mice with Lung Cancer
محورهای موضوعی : Sport Physiology
Zahra Sheykhi
1
,
Seyed Ali Hosseini
2
,
Mehrzad Moghadasi
3
1 - PhD student in the Department of Exercise Physiology, Sh.C., Islamic Azad University, Shiraz, Iran
2 - Faculty of Exercise Physiology, Marv.C., Islamic Azad University, Marvdasht, Iran
3 - Faculty of Exercise Physiology, Sh.C., Islamic Azad University, Shiraz, Iran
کلید واژه: Lung cancer, Benzo[a]pyrene, TGF-β, Swimming training , vitamin C,
چکیده مقاله :
Introduction: Lung cancer involves dysregulation of key signaling pathways, including transforming growth factor-beta (TGF-β). This study examined the effect of 12-week swim training (ST) and vitamin C (VC) supplementation on TGF-β expression in the lung tissue of mice with lung cancer.
Materials and Methods: 42 male Balb/c mice were assigned to seven groups: healthy control (HC), lung cancer control (LC), VC50, VC100, ST, ST+VC50, and ST+VC100. Lung cancer was induced by benzo[a]pyrene injection. The ST protocol was conducted for 12 weeks, 3 sessions/week. VC was administered orally daily. TGF-β mRNA expression was measured using real-time PCR. Data were analyzed by independent t-test and two-way ANOVA with Bonferroni post-hoc test (p≤0.05).
Results: Cancer induction significantly increased TGF-β expression in the LC group (2.44 ± 0.14) compared to HC (1.00 ± 0.025; p=0.001). ST alone significantly reduced TGF-β (1.76 ± 0.10) versus LC (p=0.002). A significant interaction was found between ST and VC on TGF-β reduction (p=0.028), with the lowest expression in ST+VC100 (1.05 ± 0.06) and ST+VC50 (1.12 ± 0.11) groups.
Conclusion: The combination of ST and VC synergistically reduces TGF-β expression in a lung cancer model, suggesting a promising complementary therapeutic strategy.
Introduction: Lung cancer involves dysregulation of key signaling pathways, including transforming growth factor-beta (TGF-β). This study examined the effect of 12-week swim training (ST) and vitamin C (VC) supplementation on TGF-β expression in the lung tissue of mice with lung cancer.
Materials and Methods: 42 male Balb/c mice were assigned to seven groups: healthy control (HC), lung cancer control (LC), VC50, VC100, ST, ST+VC50, and ST+VC100. Lung cancer was induced by benzo[a]pyrene injection. The ST protocol was conducted for 12 weeks, 3 sessions/week. VC was administered orally daily. TGF-β mRNA expression was measured using real-time PCR. Data were analyzed by independent t-test and two-way ANOVA with Bonferroni post-hoc test (p≤0.05).
Results: Cancer induction significantly increased TGF-β expression in the LC group (2.44 ± 0.14) compared to HC (1.00 ± 0.025; p=0.001). ST alone significantly reduced TGF-β (1.76 ± 0.10) versus LC (p=0.002). A significant interaction was found between ST and VC on TGF-β reduction (p=0.028), with the lowest expression in ST+VC100 (1.05 ± 0.06) and ST+VC50 (1.12 ± 0.11) groups.
Conclusion: The combination of ST and VC synergistically reduces TGF-β expression in a lung cancer model, suggesting a promising complementary therapeutic strategy.
1. Li C, Lei S, Ding L, et al. Global burden and trends of lung cancer incidence and mortality. Chin Med J (Engl). 2023;136(13):1583-1590.
2. Schabath MB, Cote ML. Cancer Progress and Priorities: Lung Cancer. Cancer Epidemiol Biomarkers Prev. 2019;28(10):1563-1579.
3. Hu X, Geetha RV, Surapaneni KM, et al. Lung cancer induced by Benzo(A)Pyrene: ChemoProtective effect of sinapic acid in swiss albino mice. Saudi J Biol Sci. 2021;28(12):7125-7133.
4. Farazandeh Nia, D., Hosseini, M., Riyahi Malayeri, S., Daneshjoo, A. Effect of Eight Weeks of Swimming Training with Garlic Intake on Serum Levels of IL-10 and TNF-α in Obese Male Rats. Jundishapur Scientific Medical Journal, 2018; 16(6): 665-671. doi: 10.22118/jsmj.2018.57830.Brambilla E, Gazdar A. Pathogenesis of lung cancer signalling pathways: roadmap for therapies. Eur Respir J. 2009;33(6):1485-1497.
5. Aftabi S, Barzegar Behrooz A, Cordani M, et al. Therapeutic targeting of TGF-β in lung cancer. FEBS J. 2024.
6. Infantino, V., Santarsiero, A., Convertini, P., Todisco, S., & Iacobazzi, V. (2021). Cancer Cell Metabolism in Hypoxia: Role of HIF-1 as Key Regulator and Therapeutic Target. International Journal of Molecular Sciences, 22(11), 5703.
7. Molanouri Shamsi M, Vahed A, Hekmatikar AA, Suzuki K. Combined Effects of Exercise Training and Nutritional Supplementation in Cancer Patients in the Context of the COVID-19: A Perspective Study. Front. Nutr. 2022;9:847215.
8. Fagbohun, O. F., Gillies, C. R., Murphy, K. P. J., & Rupasinghe, H. P. V. (2023). Role of Antioxidant Vitamins and Other Micronutrients on Regulations of Specific Genes and Signaling Pathways in the Prevention and Treatment of Cancer. International Journal of Molecular Sciences, 24(7), 6092.
9. Luo Z, Wan R, Liu S, et al. Mechanisms of exercise in the treatment of lung cancer - a mini-review. Front Immunol. 2023;14:1244764.
10. Esteves, M., Monteiro, M., Duarte, J. (2020). Role of Regular Physical Exercise in Tumor Vasculature: Favorable Modulator of Tumor Milieu. International Journal of Sports Medicine.
11. Li J, Liu L, Cheng Y, et al. Swimming attenuates tumor growth in CT-26 tumor-bearing mice and suppresses angiogenesis by mediating the HIF-1α/VEGFA pathway. Open Life Sci. 2022;17(1):121-130.
12. Eka Widiastuti IA, Arsyad A, Idris I, et al. Exercise adaptations and TGF-β1 levels in recreational cyclists. Ann Med Surg (Lond). 2021;70:102872.
13. Alberts, A., Moldoveanu, E.-T., Niculescu, A.-G., & Grumezescu, A. M. (2025). Vitamin C: A Comprehensive Review of Its Role in Health, Disease Prevention, and Therapeutic Potential. Molecules, 30(3), 748.
14. Villagran M, Ferreira J, Martorell M, Mardones L. The Role of Vitamin C in Cancer Prevention and Therapy: A Literature Review. Antioxidants (Basel). 2021;10(12):1894.
15. Campbell EJ, Vissers MC, Bozonet S, Dyer A, Robinson BA, Dachs GU. Restoring physiological levels of ascorbate slows tumor growth and moderates HIF-1 pathway activity in Gulo(-/-) mice. Cancer Med. 2015;4(2):303-14.
16. Guo, D., Liao, Y., Na, J., Wu, L., Yin, Y., Mi, Z., Fang, S., Liu, X., & Huang, Y. (2024). The Involvement of Ascorbic Acid in Cancer Treatment. Molecules, 29(10), 2295.
17. Piersma, B., Wouters, O., de Rond, S., Boersema, M., Gjaltema, R., Bank, R. (2017). Ascorbic acid promotes a TGFβ1‐induced myofibroblast phenotype switch. Physiological Reports. 5(18):e13324.
18. Zeng LH, Wang QM, Feng LY, Ke YD, Xu QZ, Wei AY, Zhang C, Ying RB. High-dose vitamin C suppresses the invasion and metastasis of breast cancer cells via inhibiting epithelial-mesenchymal transition. Onco Targets Ther. 2019;12:7405-7413.
19. Xiong Y, Xu S, Fu B, Tang W, Zaky MY, Tian R, Yao R, Zhang S, Zhao Q, Nian W, Lin X, Wu H. Vitamin C-induced competitive binding of HIF-1α and p53 to ubiquitin E3 ligase CBL contributes to anti-breast cancer progression through p53 deacetylation. Food Chem Toxicol. 2022;168:113321.
20. Abekova, Assima & Islamov, Rinat. (2024). ChemoProtective effects of new iodine coordinated compound in benzo[a]pyrene- induced lung cancer in BALB/c mice. BIO Web of Conferences. 100. 03001. 10.1051/bioconf/202410003001.
21. Fei Z, Li D, Li K, Zhou M, Li Y, Li Y, Sun Z.(2020). Detraining after tumor-bearing accelerates tumor growth while continuous training decreases tumor growth in mice. Journal of Traditional Chinese Medical Sciences. 7(1):75-81.
22. Lunz W, Peluzio MC, Dias CM, Moreira AP, Natali AJ. Long-term aerobic swimming training by rats reduces the number of aberrant crypt foci in 1,2-dimethylhydrazine-induced colon cancer. Braz J Med Biol Res. 2008 Nov;41(11):1000-4. doi: 10.1590/s0100-879x2008001100009. PMID: 19099153.
23. Renato Batista Paceli, Rodrigo Nunes Cal, Carlos Henrique Ferreira dos Santos, José Antonio Cordeiro , Cassiano Merussi Neiva, Kazuo Kawano Nagamine, Patrícia Maluf Cury.(2012). The influence of physical activity in the progression of experimental lung cancer in mice. Pathology - Research and Practice. Volume 208, Issue 7, 15 July 2012, Pages 377-381.
24. Xu X, Ding Y, Yang Y, Gao Y, Sun Q, Liu J, Yang X, Wang J, Zhang J.(2018). β-glucan Salecan Improves Exercise Performance and Displays Anti-Fatigue Effects through Regulating Energy Metabolism and Oxidative Stress in Mice. Nutrients.Jul 3;10(7):858. doi: 10.3390/nu10070858. PMID: 29970808; PMCID: PMC6073659.
25. Antunes LM, Darin JD, Bianchi MD. Protective effects of vitamin c against cisplatin-induced nephrotoxicity and lipid peroxidation in adult rats: a dose-dependent study. Pharmacol Res. 2000 Apr;41(4):405-11. doi: 10.1006/phrs.1999.0600. PMID: 10704263.
26. Jeon HJ, Yeom Y, Kim YS, Kim E, Shin JH, Seok PR, Woo MJ, Kim Y. Effect of vitamin C on azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colitis-associated early colon cancer in mice. Nutr Res Pract. 2018 Apr;12(2):101-109. doi: 10.4162/nrp.2018.12.2.101. Epub 2018 Mar 22. PMID: 29629026; PMCID: PMC5886961.
27. Semenza GL. Targeting HIF-1 for cancer therapy. Nat Rev Cancer. 2003 Oct;3(10):721-32. doi: 10.1038/nrc1187. PMID: 13130303.
28. Mussa A, Mohd Idris RA, Ahmed N, Ahmad S, Murtadha AH, Tengku Din TADAA, Yean CY, Wan Abdul Rahman WF, Mat Lazim N, Uskoković V, Hajissa K, Mokhtar NF, Mohamud R, Hassan R. High-Dose Vitamin C for Cancer Therapy. Pharmaceuticals (Basel). 2022 Jun 3;15(6):711. doi: 10.3390/ph15060711. PMID: 35745630; PMCID: PMC9231292.
29. Fan D, Liu X, Shen Z, Wu P, Zhong L, Lin F. Cell signaling pathways based on vitamin C and their application in cancer therapy. Biomed Pharmacother. 2023 Jun;162:114695. doi: 10.1016/j.biopha.2023.114695. Epub 2023 Apr 13. PMID: 37058822.
30. Naghizadeh, N., Riyahi Malayeri, S., Roozbahani, M., Khademi, A., Shirvani, H. The Effectiveness of Endurance Training and Nano Curcumin Supplementation on the Expression of Mir-21and P53 Genes in Brain Tumor Tissue in an Animal Model of Glioblastoma Multiform. Journal of Nutrition,Fasting and Health, 2024; 12(1): 26-35. doi: 10.22038/jnfh.2023.73964.1455
31. Ashtary-Larky D, Kashkooli S, Bagheri R, Lamuchi-Deli N, Alipour M, Mombaini D, Baker JS, Ramezani Ahmadi A, Wong A. The effect of exercise training on serum concentrations of chemerin in patients with metabolic diseases: a systematic review and meta-analysis. Arch Physiol Biochem. 2023 Oct;129(5):1028-1037. doi: 10.1080/13813455.2021.1892149. Epub 2021 Mar 2. PMID: 33651961.
