The Effect of Four-weeks Continuous and Interval Exercise Training on Activin-A Muscular Level in Female Mice with Breast Cancer

Subject Areas : Journal of Animal Biology

mona Amo-mohammadi ¹ , mandana gholami ² , Hossein Abed Natanzi ³

1 - Department of Physical Education and Sport Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran
2 - Department of Physical Education and Sport Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran
3 - Department of Physical Education and Sport Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran

Received: 2019-05-12 Accepted : 2019-10-06 Published : 2019-11-22

Keywords: Tumor, Continuous training, interval training, Cachexia, Activin-A,

Abstract :

Up-regulation of Activin-A levels in cancer patients affected by cachexia has been reported. The aim of present study was to investigate the effect of four weeks continuous and interval exercise training on Activin-A levels in muscular tissue of breast cancer bearing female mice. A total of thirty-two 6-8-week-old female Balb/c mice were randomly assigned in four groups, including: control, tumor control, interval training + tumor and continuous training + tumor groups of 8. Interval and continuous exercise training program performed for four weeks, five sessions per week on rodent special treadmill. Forty eight hours after the last exercise session, gastrocnemius muscle tissue was removed and after it was homogenized, Activin A levels were measured using ELISA method in muscular tissue. Tumor volume was also measured with digital caliper and in order to analyze data, the one-way analysis of variance test and Tukey post-hock test were used. Results of the current study showed that Activin-A levels in muscular tissue of continuous training group were significantly lower than tumor control group (p = 0.026). However, no significant difference was found in Active-A levels between the tumor control group and interval training group (p = 0.105). Gastrocnemius muscle weight in healthy control group was significantly higher compared to tumor groups (p < 0.05) and continuous and interval exercise training did not lead to significant changes in gastrocnemius muscle weight (p > 0.05). Moreover, tumor volume in continuous and interval training group was significantly lower than tumor control group (p < 0.001), but no significant difference was observed between continuous and interval training groups (p = 0.681). According to the results current study, it could be argued that exercise training, at least in the short term (four weeks), cannot exert significant effects on muscular tissue of female mice with breast cancer.

References:

1. Al-Majid S., Waters H., 2008. The biological mechanisms of cancer-related skeletal muscle wasting: the role of progressive resistance exercise. Biological research for nursing, 10(1): 7-20.

2. Alves C.R., da Cunha T.F., da Paixão N.A., Brum P.C., 2015. Aerobic exercise training as therapy for cardiac and cancer cachexia. Life sciences.. 125:9-14.

3. Bilezikjian, L. M., & Vale, W. W., 2011. The local control of the pituitary by activin signaling and modulation. Open Neuroendocrinology Journal, 4: 90-101.

4. Chen, J. L., Walton, K. L., Qian, H., Colgan, T. D., Hagg, A., Watt, M. J., ... & Gregorevic, P., 2016. Differential effects of IL6 and activin A in the development of cancer-associated cachexia. Cancer research, 76(18): 5372-5382.

5. Chen, J. L., Walton, K. L., Winbanks, C. E., Murphy, K. T., Thomson, R. E., Makanji, Y., ... & Gregorevic, P., 2014. Elevated expression of activins promotes muscle wasting and cachexia. The FASEB Journal, 28(4): 1711-1723.

6. Gilson, H., Schakman, O., Kalista, S., Lause, P., Tsuchida, K., & Thissen, J. P., 2009. Follistatin induces muscle hypertrophy through satellite cell proliferation and inhibition of both myostatin and activin. American Journal of Physiology-Endocrinology and Metabolism, 297(1): 157-164.

7. Gould, D. W., Lahart, I., Carmichael, A. R., Koutedakis, Y., & Metsios, G. S., 2013. Cancer cachexia prevention via physical exercise: molecular mechanisms. Journal of cachexia, sarcopenia and muscle, 4(2): 111-124.

8. Gulzar F, Akhtar MS, Sadiq R, Bashir S, Jamil S, Baig SM. Identifying the reasons for delayed presentation of Pakistani breast cancer patients at a tertiary care hospital. Cancer management and research. 2019; 11:1087-1096.

9. Hasani, F., Gholami, M., & Ghazalian, F., 2018. Effect of Six Weeks of Endurance Training on Tumor Volume and Muscle Myostatin Levels in Female Mice with Breast Cancer: Implications for Cachexia, ijbd, 11 (3): 44-45.

10. Hayes, J. P., & Chappell, M. A., 1990. Individual consistency of maximal oxygen consumption in deer mice. Functional Ecology, 495-503.

11. Hortobagyi, G. N., de la Garza Salazar, J., Pritchard, K., Amadori, D., Haidinger, R., Hudis, C. A., ... & O'Shaughnessy, J. A., 2005. The global breast cancer burden: variations in epidemiology and survival. Clinical breast cancer, 6(5): 391-401.

12. Høydal, M. A., Wisløff, U., Kemi, O. J., & Ellingsen, Ø., 2007. Running speed and maximal oxygen uptake in rats and mice: practical implications for exercise training. European Journal of Cardiovascular Prevention & Rehabilitation, 14(6), 753-760.

13. Hulmi, J. J., Ahtiainen, J. P., Kaasalainen, T., PöLLANEN, E. I. J. A., Hakkinen, K., Alen, M., Mero, A. A., 2007. Postexercise myostatin and activin IIb mRNA levels: effects of strength training. Medicine & Science in Sports & Exercise, 39(2): 289-297.

14. Hulmi, J. J., Oliveira, B. M., Silvennoinen, M., Hoogaars, W. M., Pasternack, A., Kainulainen, H., & Ritvos, O., 2013. Exercise restores decreased physical activity levels and increases markers of autophagy and oxidative capacity in myostatin/activin-blocked mdx mice. American Journal of Physiology-Endocrinology and Metabolism, 305(2): 171-182.

15. Jee H, Chang JE, Yang EJ. 2016. Positive prehabilitative effect of intense treadmill exercise for ameliorating cancer cachexia symptoms in a mouse model. Journal of Cancer.; 7(15): 2378-2387.

16. Jones, L. W., Viglianti, B. L., Tashjian, J. A., Kothadia, S. M., Keir, S. T., Freedland, S. J., ... & Dewhirst, M. W., 2009. Effect of aerobic exercise on tumor physiology in an animal model of human breast cancer. Journal of applied physiology, 108(2): 343-348.

17. Kainulainen H, Papaioannou KG, Silvennoinen M, Autio R2, Saarela J, Oliveira BM, 2015.Myostatin/activin blocking combined with exercise reconditions skeletal muscle expression profile of mdx mice. Mol Cell Endocrinol; 399:131-42.

18. Kazemi, A., & Mirzazadeh, E., 2018. The Effect of Endurance Training on Tumor Tissue Levels of Caspase-3 and Caspase-9 in Mice with Breast Cancer, ijbd, 11 (3): :32-43

19. Khamoui, A. V., Park, B. S., Kim, D. H., Yeh, M. C., Oh, S. L., Elam, M. L., ... & Contreras, R. J. 2016. Aerobic and resistance training dependent skeletal muscle plasticity in the colon-26 murine model of cancer cachexia. Metabolism, 65(5): 685-698.

20. Leto, G., Incorvaia, L., Badalamenti, G., Tumminello, F. M., Gebbia, N., Flandina, C., ... & Rini, G. 2006. Activin A circulating levels in patients with bone metastasis from breast or prostate cancer. Clinical & experimental metastasis, 23(2): 117-122.

21. Lira, F. S., Neto, J. C. R., & Seelaender, M., 2014. Exercise training as treatment in cancer cachexia. Applied Physiology, Nutrition, and Metabolism, 39(6): 679-686.

22. Loumaye, A., de Barsy, M., Nachit, M., Lause, P., Frateur, L., van Maanen, A., ... & Thissen, J. P., 2015. Role of Activin A and myostatin in human cancer cachexia. The Journal of Clinical Endocrinology & Metabolism, 100(5): 2030-2038.

23. Loomans HA, Andl CD. Intertwining of activin A and TGFβ signaling: dual roles in cancer progression and cancer cell invasion. Cancers. 2014; 7(1):70-91.

24. Martinelli, G. B., Olivari, D., Cecconi, A. R., Talamini, L., Ottoboni, L., Lecker, S. H., ... & Giavazzi, R. 2016. Activation of the SDF1/CXCR4 pathway retards muscle atrophy during cancer cachexia. Oncogene, 35(48): 6212-6222.

25. Matsuyama, T., Ishikawa, T., Okayama, T., Oka, K., Adachi, S., Mizushima, K., ... & Katada, K. 2015. Tumor inoculation site affects the development of cancer cachexia and muscle wasting. International journal of cancer, 137(11): 2558-2565.

26. McPherron, A., 2010. Metabolic functions of myostatin and GDF11. Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry, 10(4): 217-231.

27. Murphy, E. A., Davis, J. M., Barrilleaux, T. L., McClellan, J. L., Steiner, J. L., Carmichael, M. D., ... & Green, J. E. 2011. Benefits of exercise training on breast cancer progression and inflammation in C3 (1) SV40Tag mice. Cytokine, 55(2): 274-279.

28. Muscaritoli, M., Anker, S. D., Argiles, J., Aversa, Z., Bauer, J. M., Biolo, G., ... & Fearon, K. C. 2010. Consensus definition of sarcopenia, cachexia and pre-cachexia: joint document elaborated by Special Interest Groups (SIG) “cachexia-anorexia in chronic wasting diseases” and “nutrition in geriatrics”. Clinical Nutrition, 29(2): 154-159.

29. Pedersen, L., Idorn, M., Olofsson, G. H., Lauenborg, B., Nookaew, I., Hansen, R. H., ... & Nielsen, J., 2016. Voluntary running suppresses tumor growth through epinephrine-and IL-6-dependent NK cell mobilization and redistribution. Cell metabolism, 23(3): 554-562.

30. Penna, F., Busquets, S., Pin, F., Toledo, M., Baccino, F. M., López-Soriano, F. J., ... & Argilés, J. M., 2011. Combined approach to counteract experimental cancer cachexia: eicosapentaenoic acid and training exercise. Journal of cachexia, sarcopenia and muscle, 2(2): 95-104.

31. Shalamzari, S. A., Agha-Alinejad, H., Alizadeh, S., Shahbazi, S., Khatib, Z. K., Kazemi, A., ... & Minayi, N. 2014. 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, 17(4): 231-258.

32. Shamsi, M. M., Chekachak, S., Soudi, S., Quinn, L. S., Ranjbar, K., Chenari, J., ... & Mahdavi, M., 2017. Combined effect of aerobic interval training and selenium nanoparticles on expression of IL-15 and IL-10/TNF-α ratio in skeletal muscle of 4T1 breast cancer mice with cachexia. Cytokine, 90: 100-108.

33. Shiri, Y., Agha-Alinejad, H., Gharakhanlou, R., Amani Shalamzari, S., & Saei, M. A., 2014. Effect of six weeks endurance training on tumor tissue IL-10 cytokine levels in breast cancer bearing mice. Iranian Journal of Endocrinology and Metabolism, 16(3): 205-210.

34. Xia, Y., & Schneyer, A. L., 2009. The biology of activin: recent advances in structure, regulation and function. The Journal of endocrinology, 202(1): 1-2.

35. Zhou, X., Wang, J. L., Lu, J., Song, Y., Kwak, K. S., Jiao, Q., ... & Lacey, D. L., 2010. Reversal of cancer cachexia and muscle wasting by ActRIIB antagonism leads to prolonged survival. Cell, 142(4): 531-543.