Document Type : Original Article

Authors

1 MSc of Exercise Physiology, Faculty of Humanities, Islamic Azad University, Kerman Branch, Kerman, Iran.

2 Assistant Professor, Department of Exercise Physiology, Faculty of Sport Sciences, Kharazmi University, Karaj, Iran.

3 PhD Student of Exercise Physiology, Faculty of Sport Sciences, Shiraz University, Shiraz, Iran.

Abstract

Background and Aim: Ghrelin has a dual effect on breast cancer development. The aim of this study was to evaluate the effect of aerobic training on the level of serum and tumour tissues ghrelin in mice with breast cancer. Materials and Methods: Breast cancer cells MC4-L2 were implanted to mice and they randomly categorized into two groups including control (n=8) and training (n=8) groups. Training group performed progressive aerobic training 5 days per week for 6 weeks on treadmill and control group didn’t any training. Tumor volume was measured by a digital caliper weekly. Finally, the mice were sacrificed; serum and tumor tissue were removed and immediately frozen and kept in -70°C. Assay of ghrelin was performed by ELISA kit with code number RAB0207. Independent sample t-test and repeated measure analysis of varicance were used for extraction of results at the significance level of pResults: The results of t-test showed that the level of ghrelin in tumor (p=0.02) and serum (p=0.002) were significantly lower and higher compared to the control group. In addition, the mice heart to weight ratio was significantly higher in the training group (p=0.001) than in the control group. The result of repeated measure ANOVA showed there were significant differences between the two groups in tumor volume and food intake (p=0.001). Conclusion: According to the finding, aerobic training in tumor bearing mice have a benefits in reducing tumor volume, maintaining food intake and weight by modulating ghrelin levels in tumor tissue and serum.

Keywords

Acharyya, S., Ladner, K. J., Nelsen, L. L., Damrauer, J., Reiser, P. J., Swoap, S., & Guttridge, D. C. (2004). Cancer cachexia is regulated by selective targeting of skeletal muscle gene products. The Journal of Clinical Investigation, 114(3), 370-378. 
Almeida, P. W. M., Gomes-Filho, A., Ferreira, A. J., Rodrigues, C. E. M., Dias-Peixoto, M. F., Russo, R. C., ... & Garcia, A. M. (2009). Swim training suppresses tumor growth in mice. Journal of Applied Physiology, 107(1), 261-265.
Amani Shalamzari, S., Agha-Alinejad, H., Alizadeh, S., Shahbazi, S., Kashani Khatib, Z., 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), 231-236. 
Balkwill, F. R., & Mantovani, A. (2012). Cancer-related inflammation: common themes and therapeutic opportunities. Seminars in Cancer Biology, 22(1), 33-40.
Cassoni, P., Papotti, M., Ghè, C., Catapano, F., Sapino, A., Graziani, A., … & Muccioli, G. (2001). Identification, Characterization, and Biological Activity of Specific Receptors for Natural (Ghrelin) and Synthetic Growth Hormone Secretagogues and Analogs in Human Breast Carcinomas and Cell Lines. The Journal of Clinical Endocrinology & Metabolism, 86(4), 1738-1745. 
Chopin, L., Walpole, C., Seim, I., Cunningham, P., Murray, R., Whiteside, E., … & Herington, A. (2011). Ghrelin and cancer. Molcular and Cellular Endocrinology, 340(1), 65-69. 
DeBoer, M. D., Zhu, X. X., Levasseur, P., Meguid, M. M., Suzuki, S., Inui, A., ... & Culler, M. D. (2007). Ghrelin treatment causes increased food intake and retention of lean body mass in a rat model of cancer cachexia. Endocrinology, 148(6), 3004-3012.
Foster-Schubert, K. E., McTiernan, A., Frayo, R. S., Schwartz, R. S., Rajan, K. B., Yasui, Y., ... & Cummings, D. E. (2005). Human plasma ghrelin levels increase during a one-year exercise program. The Journal of Clinical Endocrinology & Metabolism, 90(2), 820-825.
Ghiasvand, R., Hariri, M., Haghighatdost, F., & Darvishi, l. (2013). The effect of exercise on appetite, ghrelin serum levels: implications for obesity treatment. Health System Research Journal, 9(3), 11. 
Hayes, J., & Chappell, M. (1990). Individual consistency of maximal oxygen consumption in deer mice. Functional Ecology, 495-503. 
Hoffman-Goetz, L., May, K., & Arumugam, Y. (1994). Exercise training and mouse mammary tumour metastasis. Anticancer Research, 14(6B), 2627-2631. 
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. 
Isanejad, A., Alizadeh, A. M., Shalamzari, S. A., Khodayari, H., Khodayari, S., Khori, V., & Khojastehnjad, N. (2016). Micro RNA-206, let-7a and microRNA-21 pathways involved in the anti-angiogenesis effects of the interval exercise training and hormone therapy in breast cancer. Life Sciences, 151, 30-40. 
Jeffery, P., Murray, R., Yeh, A., McNamara, J., Duncan, R., Francis, G., … & Chopin, L. (2005). Expression and function of the ghrelin axis, including a novel preproghrelin isoform, in human breast cancer tissues and cell lines. Endocrine-Related Cancer, 12(4), 839-850. 
Jones, L. W., Eves, N. D., Courneya, K. S., Chiu, B. K., Baracos, V. E., Hanson, J., … & Mackey, J. R. (2005). Effects of exercise training on antitumor efficacy of doxorubicin in MDA-MB-231 breast cancer xenografts. Clinical Cancer Research, 11(18), 6695-6698. 
Jones, L. W., Viglianti, B. L., Tashjian, J. A., Kothadia, S. M., Keir, S. T., Freedland, S. J., … & Dewhirst, M. W. (2010). Effect of aerobic exercise on tumor physiology in an animal model of human breast cancer. Journal of Applied Physiology, 108(2), 343-348.
Jones, L. W., Viglianti, B. L., Tashjian, J. A., Kothadia, S. M., Keir, S. T., Freedland, S. J., ... & Dewhirst, M. W. (2010). Effect of aerobic exercise on tumor physiology in an animal model of human breast cancer. Journal of Applied Physiology, 108(2), 343-348.
King, J. A., Wasse, L. K., Stensel, D. J., & Nimmo, M. A. (2013). Exercise and ghrelin. A narrative overview of research. Appetite, 68, 83-91.
Khori, V., Shalamzari, S. A., Isanejad, A., Alizadeh, A. M., Alizadeh, S., Khodayari, S., ... & Khaniki, M. (2015). Effects of exercise training together with tamoxifen in reducing mammary tumor burden in mice: Possible underlying pathway of miR-21. European Journal of Pharmacology, 765, 179-187.
Kojima, M., Hosoda, H., Date, Y., Nakazato, M., Matsuo, H., & Kangawa, K. (1999). Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature, 402(6762), 656-660. 
Leidy, H., Gardner, J., Frye, B., Snook, M., Schuchert, M., Richard, E., & Williams, N. (2004). Circulating ghrelin is sensitive to changes in body weight during a diet and exercise program in normal-weight young women. The Journal of Clinical Endocrinology & Metabolism, 89(6), 2659-2664. 
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.
Ravussin, E., Tschöp, M., Morales, S., Bouchard, C., & Heiman, M. L. (2001). Plasma ghrelin concentration and energy balance: overfeeding and negative energy balance studies in twins. The Journal of Clinical Endocrinology & Metabolism, 86(9), 4547-4547. 
Schmidt, A., Maier, C., Schaller, G., Nowotny, P., Bayerle-Eder, M., Buranyi, B., ... & Wolzt, M. (2004). Acute exercise has no effect on ghrelin plasma concentrations. Hormone and Metabolic Research, 36(03), 174-177. 
Stefanaki, C., Rorris, F. P., & Stamatakos, M. (2012). The Role of Ghrelin Signals in Breast Cancer-A Systematic Review. Current Signal Transduction Therapy, 7(3), 247-253. 
Takano, H., Morita, T., Iida, H., Asada, K. I., Kato, M., Uno, K., ... & Eto, F. (2005). Hemodynamic and hormonal responses to a short-term low-intensity resistance exercise with the reduction of muscle blood flow. European Journal of Applied Physiology, 95(1), 65-73.
Tisdale, M. J. (2009). Mechanisms of cancer cachexia. Physiological Reviews, 89(2), 381-410. 
Wang, W., Andersson, M., Iresjo, B., Lonnroth, C., & Lundholm, K. (2006). Effects of ghrelin on anorexia in tumor-bearing mice with eicosanoid-related cachexia. International Journal of Oncology, 28(6), 1393-1400. 
Wolf, I., Sadetzki, S., Kanety, H., Kundel, Y., Pariente, C., Epstein, N., ... & Shimon, I. (2006). Adiponectin, ghrelin, and leptin in cancer cachexia in breast and colon cancer patients. Cancer, 106(4), 966-973.
Woods, J. A., Davis, J. M., Kohut, M. L., Ghaffar, A., Mayer, E. P., & Pate, R. R. (1994). Effects of exercise on the immune response to cancer. Medicine and Science in Sports and Exercise, 26(9), 1109.
Zielinski, M. R., Muenchow, M., Wallig, M. A., Horn, P. L., & Woods, J. A. (2004). Exercise delays allogeneic tumor growth and reduces intratumoral inflammation and vascularization. Journal of Applied Physiology, 96(6), 2249-2256.