Comparison of the effect of 6-week aerobic and high intensity interval training on expression of uPA and uPAR in the tumor tissue of female mice with breast cancer

Document Type : Original Article

Authors

1 Department of Sport Sciences, University of Tehran, Kish International Campus, Kish, Iran

2 Department of Exercise Physiology, Faculty of Sport Sciences and Health, University of Tehran, Tehran, Iran

Abstract

Background and Objective: In the past few decades, research on the role of physical activity in the prevention of cancer and disease progression has been the subject of attention of many researchers. The aim of this study was to compare the effect of 6 weeks of aerobic training and high intensity interval training on the expression of uPA and uPAR in the tumor tissue of female mice with breast cancer.
Materials and Methods: 24 female Balb c mice with breast cancer were randomly divided into 3 groups: tumor (T), tumor + aerobic training (T+AE) and tumor + high intensity interval training (T+HIIT). The T+AE group had incremental endurance treadmill running for 6 weeks/5 days/60 minutes. The T+HIIT group had a 6-week/3-day/60 min high intensity interval training protocol. Then, the mice were killed, the tumor tissue was removed and frozen in liquid nitrogen. The expression of uPA and uPAR genes was measured by Real Time-PCR method. ΔCT, ΔΔCT, fold change, one-way ANOVA and Tukey's tests were performed at a significant level P<0.05 with GENEX software .
Results: The results of the present study showed that in the T+AE group compared to the T group, the expression of uPA and uPAR decreased (P=0.00) 2.07 and 2.55 times. In the T+HIIT group compared to the T group, the expression of uPA and uPAR decreased 4.25 and 7.74 times (P=0.00), and in the T+HIIT group compared to the T+AE group, the expression of uPA and uPAR decreased 2.04 and 3.03 times (P=0.00).
Conclusion: Aerobic training and high intensity interval training are probably effective in preventing the progression of breast cancer by reducing the expression of uPA and uPAR.

Keywords

Main Subjects

References

  1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: a Cancer Journal for Clinicians 2021;71(3):209-49.
  2. Sharma GN1, Dave R, Sanadya J, Sharma P, Sharma KK. Various types and management of breast cancer: an overview. J Adv Pharm Technol Res. 2010;1(2):109-26.
  3. Lv T, Zhao Y, Jiang X, Yuan H, Wang H, Cui X, et al. uPAR: An Essential Factor for Tumor Development. Journal of Cancer 2021;12(23):7026-40.
  4. Masucci MT, Minopoli M, Carluccio GD, Carluccio ML, Carriero MV. Therapeutic Strategies Targeting Urokinase and Its Receptor in Cancer. Cancers 2022;14(3):498.
  5. Vassalli JD, Baccino D, Belin D. A cellular binding site for the Mr 55,000 form of the human plasminogen activator, urokinase. J Cell Biol. 1985;100:86–
  6. Ismail AA, Shaker BT, Bajou K. The Plasminogen-Activator Plasmin System in Physiological and Pathophysiological Angiogenesis. International Journal of Molecular Sciences 2021;23(1).
  7. Gogineni VR, Nalla AK, Gupta R, Dinh DH, Klopfenstein JD, Rao JS. Chk2-mediated G2/M cell cycle arrest maintains radiation resistance in malignant meningioma cells. Cancer Lett 2011; 313: 64-75.
  8. Mekkawy AH, Pourgholami MH, Morris DL. Involvement of urokinase-type plasminogen activator system in cancer: an overview. Medicinal Research Reviews 2014;34(5):918-56.
  9. Gao X, Guo Q, Wang S, Gao C, Chen J, Zhang L, et al. Silencing of uPAR via RNA interference inhibits invasion and migration of oral tongue squamous cell carcinoma. Oncol Lett 2018; 16: 3983-91.
  10. D'Alessio S, Blasi F. The urokinase receptor as an entertainer of signal transduction. Front Biosci (Landmark Ed). 2009; 14: 4575-87.
  11. Santibanez JF, Obradović H, Kukolj T, Krstić J. Transforming growth factor-β, matrix metalloproteinases, and urokinase-type plasminogen activator interaction in the cancer epithelial to mesenchymal transition. Dev Dyn. 2018; 247: 382-95.
  12. Masi I, Caprara V, Bagnato A, Rosanò L. Tumor Cellular and Microenvironmental Cues Controlling Invadopodia Formation. Front Cell Dev Biol. 2020; 8: 584181.
  13. Herkenne S, Paques C, Nivelles O, LionM, Bajou K, Pollenus T, et al. The interaction of uPAR with VEGFR2 promotes VEGF-induced angiogenesis. Sci Signal. 2015; 8: ra117.
  14. Hojman P, Gehl J, Christensen JF, Pedersen BK. Molecular Mechanisms Linking Exercise to Cancer Prevention and Treatment. Cell Metabolism 2018;27(1):10-21.
  15. Amani-Shalamzari S, Agha-Alinejad H, Alizadeh S, et al. The effect of exercise training on the level of tissue IL-6 and vascular endothelial growth factor in breast cancer bearing mice. Iranian Journal of Basic Medical Sciences 2014; 17(4):231-6.
  16. Schebeleski-Soares C, Occhi-Soares RC, Franzoi-de-Moraes SM, et al. Preinfection aerobic treadmill training improves resistance against Trypanosoma cruzi infection in mice. Appl Physiol Nutr Metab. 2009;34(4):659-665.
  17. Marcinko KA, Sikkema SA, Samaan CO, et al. High intensity interval training improves liver and adipose tissue insulin sensitivity. Molecular Metabolism 2015;4(12):903-915.
  18. Jones LW, Viglianti BL, Tashjian JA, et al. Effect of aerobic exercise on tumor physiology in an animal model of human breast cancer. J Appl Physiol. 2010;108(2):343-348.
  19. Rohde C, Polcwiartek C, Andersen E, Vang T, Nielsen J. Effect of a physical activity intervention on suPAR levels: A randomized controlled trial. Journal of Science and Medicine in Sport 2018;21(3):286-90.
  20. Dooijewaard G, de Boer A, Turion PN, Cohen AF, Breimer DD, Kluft C. Physical exercise induces enhancement of urokinase-type plasminogen activator (u-PA) levels in plasma. Thrombosis and Haemostasis 1991;65(1):82-6.
  21. Gustafsson A, Ventorp F, Wisen AG, Ohlsson L, Ljunggren L, Westrin A. Effects of Acute Exercise on Circulating Soluble Form of the Urokinase Receptor in Patients With Major Depressive Disorder. Biomarker Insights 2017;12:1177271917704193.
  22. Koelwyn GJ, Quail DF, Zhang X, White RM, Jones LW. Exercise-dependent regulation of the tumour microenvironment. Nat Rev Cancer. 2017;17(10):620-32.
  23. Yoon SY, Lee YJ, Seo JH, Sung HJ, Park KH, Choi IK, Kim SJ, Oh SC, Choi CW, Kim BS, et al. uPAR expression under hypoxic conditions depends on iNOS modulated ERK phosphorylation in the MDA-MB-231 breast carcinoma cell line. Cell Res. 2006; 16(10).
  24. Chen J, Ding ZY, Li S, Liu S, Xiao C, Li Z, et al. Targeting transforming growth factor-β signaling for enhanced cancer chemotherapy. Theranostics 2021; 11: 1345-63.
  25. Koelwyn GJ, Quail DF, Zhang X, White RM, Jones LW. Exercise-dependent regulation of the tumour microenvironment. Nat Rev Cancer. 2017;17(10):620-32.
Daneshvar Medicine
Volume 31, Issue 5 - Serial Number 168
January and February 2024
Pages 23-34

Files

Share

How to cite

Statistics