اثر 6 هفته تمرین هوازی بر سطوح گرلین در بافت تومور و سرم موش های مبتلا به سرطان پستان

نوع مقاله: مقاله پژوهشی

نویسندگان

1 کارشناس ارشد فیزیولوژی ورزشی، دانشکده ادبیات و علوم انسانی، دانشگاه آزاد اسلامی، واحد کرمان، کرمان، ایران.

2 استادیار گروه فیزیولوژی ورزشی، دانشکده علوم ورزشی، دانشگاه خوارزمی، کرج، ایران.

3 دانشجوی دکترای فیزیولوژی ورزشی، دانشکده علوم ورزشی، دانشگاه شیراز، شیراز، ایران.

چکیده

زمینه و هدف: گرلین نقش دوگانه­ای در توسعه سرطان پستان دارد. هدف از تحقیق حاضر بررسی اثر تمرینات هوازی بر سطوح سرمی و بافتی گرلین در موش­های حامل سرطان پستان بود. روشتحقیق: تومور سرطان پستان وابسته به گیرنده استروژن ناشی از سلول ‌سرطانی MC4-L2 به 16 سر موش­ بالب-C پیوند زده شد و در ادامه موش ها به صورت تصادفی در دو گروه کنترل (8 سر) و تمرین (8 سر) قرار گرفتند. گروه تمرین به مدت 6 هفته، 5 روز در هفته تمرینات هوازی فزآینده روی نوارگردان را اجرا کردند و گروه کنترل هیچ­گونه فعالیتی انجام ندادند. حجم تومور موش­ها به صورت هفتگی با کولیس دیجیتال اندازه­گیری شد. در پایان موش­ها قربانی شده و سرم و بافت تومور آن ها برداشته شد و در دمای 70- درجه سانتی گراد نگهداری گردید. سنجش گرلین با استفاده از کیت الایزا با کد  RAB0207صورت گرفت. از آزمون t مستقل و تحلیل واریانس با اندازه گیری مکرر برای تحلیل و تفسیر یافته ­ها استفاده شد و سطح معنی­ داری 0/05 >p در نظر گرفته شد. یافتهها: بر اساس نتایج آزمون t مستقل، مقدار گرلین درون تومور (0/02=p) و سرم (0/002 =p) در گروه تمرین نسبت به گروه کنترل به ترتیب پایین­ تر و بالاتر بود. به علاوه، نسبت وزن قلب به وزن موش ­ها (0/001=p) در گروه تمرین نسبت به گروه کنترل به طور معنی دار بالاتر بود. نتایج آزمون تحلیل واریانس با اندازه گیری مکرر نیز برای حجم تومور و غذای مصرفی حاکی از اختلاف معنی­ دار بین دو گروه بود (0/001 =p). نتیجهگیری: با توجه به نتایج بدست آمده، تمرینات هوازی در موش­های حامل تومور، از طریق تعدیل سطوح گرلین در بافت تومور و سرم، اثرات مفیدی در کاهش حجم تومور، حفظ مصرف غذا و کنترل وزن دارد.

کلیدواژه‌ها


عنوان مقاله [English]

Effects of 6 weeks of aerobic training on the level of serum and tumour tissues ghrelin in mice with breast cancer

نویسندگان [English]

  • Marzieh Shadravan 1
  • Sadegh Amani-Shalamzari 2
  • Ali Sarikhani 3
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.
چکیده [English]

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.

کلیدواژه‌ها [English]

  • Aerobic training
  • Estrogen receptor dependent breast cancer
  • Appetizer Peptide
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.