The effect of exercise training on the level of tissue IL-6 and vascular endothelial growth factor in breast cancer bearing mice

Document Type : Original Article

Authors

1 Physical Education Department, Faculty of Humanities, Tarbiat Modares University, Tehran, Iran

2 Hematology Department, Allied Medical School, Tehran University of Medical Sciences, Tehran, Iran

3 Medical Genetics Department, Faculty of Medical Sciences, ,Tarbiat Modares University, Tehran, Iran

Abstract

Objective(s): The goal of this study was assessing the prophylactic effect of exercise and its role as an adjuvant therapy on level of cytokines involved in angiogenesis in estrogen-dependent breast cancer.
Materials and Methods: Forty female BALB/c mice were randomly assigned to exercise-tumor-exercise (ETE), exercise-tumor-rest (ETR), rest-tumor-exercise (RTE) and rest-tumor-rest (RTR) groups. After orientation in the environment, two groups of mice performed continuous endurance exercise for 8 weeks, and thereafter estrogen-dependent MC4L2 cancer cells were injected to them. Then, one group of each of trained and non-trained mice performed endurance exercise 5 days per week for 6 weeks. Tumor volume was measured by a digital caliper weekly. Finally, the mice were sacrificed; tumor tissue was removed, immediately frozen and kept in              -70°C. Tumor sample was homogenized; levels of cytokines were measured and quantified using ELISA.
Results: There was significant reduction in the level of interlukin-6 (IL-6) (P=0.001), Vascular endothelial growth factor (VEGF) (P=0.0001) and tumor volume (P=0.0001) among the groups performing endurance exercise after malignancy (RTE and ETE) in comparison with groups not performing endurance exercise (ETR and RTR), and these results were in agreement with tumor growth rate.
Conclusion: Exercise can cause reduction in levels of pro-inflammatory cytokines in tumor tissue. Decreased IL-6 production could reduce the generation of VEGF, resulting in reduced intra-tumor angiogenesis. Due to reduction of the level of these cytokines in groups doing exercise before and after malignancy, exercise is presumed to be an adjuvant therapy in estrogen-receptor dependent tumors in addition to its effective prophylactic role.

Keywords

References

1. Siegel R, Naishadham D, Jemal A. Cancer statistics 2013. CA  Cancer J Clin 2013; 63:11-30.
2. Ebrahimi M, Vahdaninia M, Montazeri A. Risk factors for breast cancer in Iran: a case-control study. Breast Cancer Res 2002; 4:R10.
3. Harirchi I, Ebrahimi M, Zamani N, Jarvandi S, Montazeri A. Breast cancer in Iran: a review of 903 case records. Public Health 2000; 114:143-145.
4. Hoffman-Goetz L. Physical activity and cancer prevention: animal-tumor models. Med Sci Sports Exerc 2003; 35:1828-1833.
5. Lanari C, Lüthy I, Lamb CA, Fabris V, Pagano E, Helguero LA, et al. Five novel hormone-responsive cell lines derived from murine mammary ductal carcinomas: in vivo and in vitro effects of estrogens and progestins. Cancer Res 2001; 61:293-302.
6. Pedersen BK. Exercise-induced myokines and their role in chronic diseases. Brain Behav Immun 2011; 25:811-816.
7. Lee IM. Physical activity and cancer prevention-data from epidemiologic studies. Med Sci Sports Exerc 2003; 35:1823-1827.
8. Na HK, Oliynyk S. Effects of physical activity on cancer prevention. Ann N Y Acad Sci 2011; 1229:176-183.
9. Montaruli A, Patrini P, Roveda E, Carandente F. Physical activity and breast cancer. Sport Sci Health 2012; 8:1-13.
10. Friedenreich CM, Cust AE. Physical activity and breast cancer risk: impact of timing, type and dose of activity and population subgroup effects. Br J Sports Med 2008; 42:636-647.
11. Jones LW, Antonelli J, Masko EM, Broadwater G, Lascola CD, Fels D, et al. Exercise modulation of the host-tumor interaction in an orthotopic model of murine prostate cancer. J Appl Physiol 2012; 113:263-272.
12. Murphy EA, Davis JM, Barrilleaux T, McClellan J, Steiner J, Carmichael M, et al. Benefits of exercise training on breast cancer progression and inflammation in C3 (1) SV40Tag mice. Cytokine 2011; 55:274-279.
13. Zielinski MR, Muenchow M, Wallig MA, Horn PL, Woods JA. Exercise delays allogeneic tumor growth and reduces intratumoral inflammation and vascularization. J Appl Physiol 2004; 96:2249-2256.
14. Thompson HJ, Jiang W, Zhu Z. Candidate mechanisms accounting for effects of physical activity
on breast carcinogenesis. IUBMB Life 2009; 61:895-901.
15. Hong DS, Angelo LS, Kurzrock R. Interleukin-6 and its receptor in cancer. Cancer 2007; 110:1911-1928.
16. Sullivan NJ. Interleukin-6 in the Breast Tumor Microenvironment. In: Gunduz M, Gunduz E, editors. Breast Cancer - Focusing Tumor Microenvironment, Stem cells and Metastasis: InTech. 2011. p. 584.
17. Honma S, Shimodaira K, Shimizu Y, Tsuchiya N, Saito H, Yanaihara T, et al. The influence of inflammatory cytokines on estrogen production and cell proliferation in human breast cancer cells. Endocrin J 2002; 49:371-377.
18. Longatto Filho A, Lopes J, Schmitt FC. Angiogenesis and breast cancer. J Oncol 2010; 2010.
19. Purohit A, Newman SP, Reed MJ. The role of cytokines in regulating estrogen synthesis: implications for the etiology of breast cancer. Breast Cancer Res 2002; 4:65-69.
20. Dethlefsen C, Højfeldt G, Hojman P. The role of intratumoral and systemic IL-6 in breast cancer. Breast Cancer Res Treat 2013; 1-8.
21. Schneider BP, Miller KD. Angiogenesis of breast cancer. J Clin Oncol 2005; 23:1782-1790.
22. Ghaderi A, Hosseini A, Jaberipour M, Razmkhah M. Os-13: VEGF, IL-8 and MMP2 expression profile in adipose-derived stem cells (ASCs) of breast cancer patients. Cell J (Yakhteh‎)2010;1-2.
23. Lee K, Qian DZ, Rey S, Wei H, Liu JO, Semenza GL. Anthracycline chemotherapy inhibits HIF-1 transcriptional activity and tumor-induced mobilization of circulating angiogenic cells. Proc Natl Acad Sci 2009; 106:2353-2358.
24. Jones LW, Viglianti BL, Tashjian JA, Kothadia SM, Keir ST, Freedland SJ, et al. Effect of aerobic exercise on tumor physiology in an animal model of human breast cancer. J Appl Physiol 2010; 108:343-348.
25. Iliopoulos D, Hirsch HA, Struhl K. An epigenetic switch involving NF-κB, Lin28, Let-7 MicroRNA, and IL6 Links inflammation to cell transformation. Cell 2009; 139:693-706.
26. Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow?  Lancet 2001; 357:539-545.
27. Betof AS, Dewhirst MW, Jones LW. Effects and potential mechanisms of exercise training on cancer progression: a translational perspective. Brain Behav Immun 2013; 30:S75-87
28. Donatto F, Neves R, Rosa F, Camargo R, Ribeiro H, Matos-Neto E, et al. Resistance exercise modulates lipid plasma profile and cytokine content in the adipose tissue of tumour-bearing rats. Cytokine 2013; 61:426-432.
29. Paul-Pletzer K. Tocilizumab: blockade of interleukin-6 signaling pathway as a therapeutic strategy for inflammatory disorders. Drugs Today 2006; 42:559-576.
30. Benoy I, Salgado R, Colpaert C, Weytjens R, Vermeulen PB, Dirix LY. Serum interleukin 6, plasma VEGF, serum VEGF, and VEGF platelet load in breast cancer patients. Clin Breast Cancer 2002; 2:311-315.

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