Effects of Aerobic Exercise on Cytokine Expression in a Breast Cancer Mouse Model

  • Bangsub LEE LEE Department of College of General Education, Chung-Ang University, Seoul, Republic of Korea
  • Wooyoung CHUNG Department of College of General Education, Chung-Ang University, Seoul, Republic of Korea
Breast cancer, C-reactive protein, Cytokine, Inflammation, Interleukin


Background: Regular physical activity lowers or prevents the risk of heart disease, diabetes, some cancers, the development of hypertension, and death from these diseases through a reduction in inflammation. Cytokines, such as interleukin (IL)-6, IL-18, tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP) are major markers representing the inflammatory process. This study aimed to investigate cytokine mRNA expression levels of IL-6, IL-18, TNF-α, and CRP in hepatocytes from breast cancer xenograft mice with or without moderate exercise.

Methods: Each of the 5 mice at SP Korea Company, Seoul, Korea in 2015 were randomly divided into 3 groups: control (CTL), breast cancer (BC), and breast cancer exercise (BCEX). The inflammatory markers were analyzed in 10-week-old female Balb/C nude mice hepatocytes (n = 15; CTL = 5, BC = 5, BCEX = 5). Moderate intensity physical activity in mice was performed on a treadmill at an intensity of 18 m/min for 12 weeks, at 30 min for 5 days per week.

Results: IL-6, IL-18, TNF-α, and CRP mRNA expression levels of the BCEX group were significantly decreased compared to those of the BC group (P < 0.05), with no difference to the CTL group.

Conclusion: There might be a reduced inflammatory process via a reduction in TNF-α, IL-6, IL-18, and CRP expression in breast cancer mice that were subjected to moderate intensity exercise.


1. Murphy EA, Enos RT, Velázquez KT (2015). Influence of exercise on inflammation in cancer: direct effect or innocent bystander? Exerc Sport Sci Rev, 43(3), 134-142.
2. Katapodi MC, Viassolo V, Caiata-Zufferey M et al (2017). Cancer predisposition cascade screening for hereditary breast/ovarian cancer and Lynch syndromes in Switzerland: study protocol. JMIR Res Protoc, 6(9), e184.
3. Steiner JL, Davis JM, McClellan JL et al (2013). Effects of voluntary exercise on tumorigenesis in the C3 (1)/SV40Tag transgenic mouse model of breast cancer. Int J Oncol, 42(4), 1466-1472.
4. McClellan JL, Steiner JL, Day SD et al (2014). Exercise effects on polyp burden and immune markers in the ApcMin/+ mouse model of intestinal tumorigenesis. Int J Oncol, 45(2), 861-868.
5. Zimmer P, Baumann FT, Oberste M et al (2018). Influence of personalized exercise recommendations during rehabilitation on the sustainability of objectively measured physical activity levels, fatigue, and fatigue-related biomarkers in patients with breast cancer. Integr Cancer Ther, 17(2), 306-311.
6. Colbert LH, Westerlind KC, Perkins SN et al (2009). Exercise effects on tumorigenesis in a p53-deficient mouse model of breast cancer. Med Sci Sports Exerc, 41(8), 1597-605.
7. Aoi W, Naito Y, Takagi T et al (2013). A novel myokine, secreted protein acidic and rich in cysteine (SPARC), suppresses colon tumorigenesis via regular exercise. Gut, 62(6), 882-889.
8. Baltgalvis KA, Berger FG, Peña MMO et al (2008). Effect of exercise on biological pathways in Apc Min/+ mouse intestinal polyps. J Appl Physiol(1985), 104(4), 1137-1143.
9. Murphy EA, Davis JM, Barrilleaux TL et al (2011). Benefits of exercise training on breast cancer progression and inflammation in C3 (1) SV40Tag mice. Cytokine, 55(2), 274-279.
10. World Cancer Research Fund; American Institute for Cancer Research. Breast cancer: how diet, nutrition, and physical activity affect breast cancer risk. https://www.wcrf.org/dietandcancer/breast-cancer
11. Zhu Z, Jiang W, Zacher JH et al (2012). Effects of energy restriction and wheel running on mammary carcinogenesis and host systemic factors in a rat model. Cancer Prev Res (Phila), 5(3), 414-422.
12. Lynch BM, Friedenreich CM, Winkler EA et al (2011). Associations of objectively assessed physical activity and sedentary time with biomarkers of breast cancer risk in postmenopausal women: findings from NHANES (2003–2006). Breast Cancer Res Treat, 130(1), 183-194.
13. Grivennikov SI, Greten FR, Karin M (2010). Immunity, inflammation, and cancer. Cell, 140(6), 883-899.
14. Vona-Davis L, Rose DP (2007). Adipokines as endocrine, paracrine, and autocrine factors in breast cancer risk and progression. Endocr Relat Cancer, 14(2), 189-206.
15. You T, Arsenis NC, Disanzo BL et al (2013). Effects of exercise training on chronic inflammation in obesity. Sports Med, 43(4), 243-256.
16. Golbidi S, Laher I (2014). Exercise induced adipokine changes and the metabolic syndrome. J Diabetes Res, 2014:726861.
17. Rogers LQ, Fogleman A, Trammell R et al (2013). Effects of a physical activity behavior change intervention on inflammation and related health outcomes in breast cancer survivors: pilot randomized trial. Integr Cancer Ther, 12(4), 323-335.
18. Jones SB, Thomas GA, Hesselsweet SD et al (2013). Effect of exercise on markers of inflammation in breast cancer survivors: the Yale exercise and survivorship study. Cancer Prev Res (Phila), 6(2), 109-118.
19. Aoi W, Naito Y, Takagi T et al (2010). Regular exercise reduces colon tumorigenesis associated with suppression of iNOS. Biochem Biophys Res Commun, 399(1), 14-19.
20. Akahira JI, Konno R, Ito K et al (2004). Impact of serum interleukin-18 level as a prognostic indicator in patients with epithelial ovarian carcinoma. Int J Clin Oncol, 9(1), 42-46.
21. Nicolini A, Carpi A, Rossi G (2006). Cytokines in breast cancer. Cytokine Growth Factor Rev, 17(5), 325-337.
22. Papanicolaou DA, Wilder RL, Manolagas SC et al (1998). The pathophysiologic roles of interleukin-6 in human disease. Ann Intern Med, 128(2), 127-137.
23. Falconer JS, Fearon KC, Ross JA et al (1995). Acute-phase protein response and survival duration of patients with pancreatic cancer. Cancer, 75(8), 2077-2082.
24. Legouffe E, Rodriguez C, Picgt MC et al (1998). C-reactive protein serum level is a valuable and simple prognostic marker in non Hodgkin's lymphoma. Leuk Lymphoma, 31(3-4), 351-357.
25. Nozoe T, Saeki H, Sugimachi K (2001). Significance of preoperative elevation of serum C-reactive protein as an indicator of prognosis in esophageal carcinoma. Am J Surg, 182(2), 197-201.
26. Staal-van den Brekel AJ, Dentener MA, Schols AM et al (1995). Increased resting energy expenditure and weight loss are related to a systemic inflammatory response in lung cancer patients. J Clin Oncol, 13(10), 2600-2605.
27. Miki C, Konishi N, Ojima E et al (2004). C-reactive protein as a prognostic variable that reflects uncontrolled up-regulation of the IL-1-IL-6 network system in colorectal carcinoma. Dig Dis Sci, 49(6), 970-976.
How to Cite
LEE BL, CHUNG W. Effects of Aerobic Exercise on Cytokine Expression in a Breast Cancer Mouse Model. Iran J Public Health. 49(1):14-20.
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