Document Type : Research Paper
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Abstract
The aim of this study was to assess The effects of aerobic training on Nf-kB, Lin28B and let-7a microRNA expressions and levels of tumor tissue IL-6 in mice with breast cancer. Twenty BALB/c c mice (4-5 weeks,17g mass) were cancerous by injection of estrogen-dependent receptor breast cancer cells MC4-L2 and divided into two groups: tumor-training(TT) and tumor-control(TC) group. Then TT group completed aerobic training for 6 weeks, 5 days per week (14-18 m/min). 48 hours after the last exercise subjects were sacrificed. Tissue sampling were collected and stored in -70ᵒ. Nf-kB, Lin28B and let-7a microRNA expressions were accounted with Real time-PCR and IL-6 levels was accounted with ELISA Kit. Repeated measures and independent t tests were used to assess tumor size and IL-6, respectively. Statistical analysis of Nf-kB, Lin28B and let-7a were conducted by REST software. Tumor size, Nf-kB, Lin28B and IL-6 levels were significantly decreased in TT group compare with TC group (p<0.05). microRNA let-7a was significantly increased in TT against control group respectively (p=0.000). In breast cancer, a positive feedback loop consisting of Nf-kB, Lin28B, microRNA let-7a and IL-6 is activated. It seems that regarding to the depressing effects of aerobic training on this regulatory circuit in mice with breast cancer, This type of training can be used as adjuvant therapy in conjunction with other therapies for estrogen receptor dependent breast cancer.
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1) فرج اللهی معصومه. روشهای بهکارگرفتهشده جهت تسکین شدت خستگی توسط بیماران مبتلا به سرطان تحت شیمی‌درمانی. نشریۀ پرستاری ایران. 2004؛ 17(38): 64ـ58.
2) Siegel R, Naishadham D, Jemal A. Cancer statistics. CA: A Cancer Journal for Clinicians. 2013; 63(1): 11-30.
3) Amani-Shalamzari S, Agha-Alinejad H, Alizadeh S, Shahbazi S, Khatib Z K, Kazemi A, 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.
4) Ligibel J A, Giobbie-Hurder A, Olenczuk D, Campbell N, Salinardi T, Winer E P, et al. Impact of a mixed strength and endurance exercise intervention on levels of adiponectin, high molecular weight adiponectin and leptin in breast cancer survivors.Cancer Causes & Control. 2009; 20(8): 1523-8.
5) Zielinski M R, Muenchow M, Wallig M A, Horn P L, Woods J A. Exercise delays allogeneic tumor growth and reduces intratumoral inflammation and vascularization. Journal of Applied Physiology. 2004; 96(6): 2249-56.
6) Murphy E A, Davis J M, 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(2): 274-9.
7) Thompson H J. Effects of physical activity and exercise on experimentally-induced mammary carcinogenesis. Breast Cancer Research and Treatment. 1997; 46(2-3): 135-41.
8) صالحیان امید، سوری رحمان، حسن زهیر. مقایسۀ تأثیر دو نوع تمرین هوازی استقامتی پیوسته و منقطع بر سطوح پروتئین شوک حرارتی 70 در موش‌های با تومور سرطان سینه. نشریۀ فیزیولوژی ورزشی. 1391؛ 4(15): 20ـ109.
9) Woods J A, Vieira V J, Keylock K T. Exercise, inflammation, and innate immunity. Immunology and Allergy Clinics of North America. 2009; 29(2): 381-93.
10) Iliopoulos D, Hirsch H A, Struhl K. An epigenetic switch involving NF-κB, Lin28, Let-7 MicroRNA, and IL6 links inflammation to cell transformation. Cell. 2009; 139(4): 693-706.
11) Taniguchi K, Karin M. IL-6 and related cytokines as the critical lynchpins between inflammation and cancer. Seminars in Immunology. 2014; 26: 54–74.
12) Ross S A, Davis C D. MicroRNA, nutrition, and cancer prevention. Advances in Nutrition: An International Review Journal. 2011; 2(6): 472-85.
13) Boyerinas B, Park S M, Hau A, Murmann A E, Peter M E. The role of let-7 in cell differentiation and cancer. Endocrine-Related Cancer. 2010; 17(1): 19-36.
14) Esquela-Kerscher A, Trang P, Wiggins J F, Patrawala L, Cheng A, Ford L, et al. The let-7 microRNA reduces tumor growth in mouse models of lung cancer. Cell Cycle-Landes Bioscience. 2008; 7(6): 759.
15) Viswanathan S R, Daley G Q, Gregory R I. Selective blockade of microRNA processing by Lin28. Science. 2008; 320(5872): 97-100.
16) Hong D S, Angelo L S, Kurzrock R. Interleukin‐6 and its receptor in cancer. Cancer. 2007; 110(9): 1911-28.
17) Thompson H J, Jiang W, Zhu Z. Candidate mechanisms accounting for effects of physical activity on breast carcinogenesis. IUBMB Life. 2009; 61(9): 895-901.
18) آقاعلی‌نژاد حمید، توفیقی اصغر، زهیر محمدحسن، مهدوی مهدی، شاهرخی سمیه. اثر تمرین استقامتی پیوسته بر میزان HSP70 و طول عمر موش‌های مبتلا به تومور سرطان سینه. نشریۀ المپیک .1387؛ 16(2):86ـ75.
19) Lanari C, Lüthy I, Lamb C A, Fabris V, Pagano E, Helguero L A, 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 Research. 2001; 61(1): 293-302.
20) Jones L W, Viglianti B L, Tashjian J A, Kothadia S M, Keir S T, Freedland S J, et al. Effect of aerobic exercise on tumor physiology in an animal model of human breast cancer. Journal of Applied Physiology. 2010; 108(2): 343-8.
21) Enoki T, Yoshida Y, Lally J, Hatta H, Bonen A. Testosterone increases lactate transport, monocarboxylate transporter (MCT) 1 and MCT4 in rat skeletal muscle. The Journal of Physiology. 2006; 577(1): 433-43.
22) آقاعلی‌نژاد حمید. اثر یک دوره تمرین استقامتی بر بیان mir-155 و بیان ژن SOCS1 در تومور موش‌های مادۀ مبتلا به سرطان پستان. فصلنامۀ علمی ـ پژوهشی بیماری‌های پستان. 1392؛ 6(4) : 14ـ7.
23) Balkwill F, Mantovani A. Inflammation and cancer: Back to Virchow? The Lancet. 2001; 357(9255): 539-45.
24) Verma V K, Singh V, Singh M P, Singh S M. Effect of physical exercise on tumor growth regulating factors of tumor microenvironment: Implications in exercise-dependent tumor growth retardation. Immunopharmacology and Immunotoxicology. 2009; 31(2): 274-82.
25) Cuevas M J, Almar M, García-Glez J C, García-López D, De Paz J A, Alvear-Órdenes I, et al. Changes in oxidative stress markers and NF-κB activation induced by sprint exercise. Free Radical Research. 2005; 39(4): 431-9.
26) Gius D, Spitz D R. Redox signaling in cancer biology. Antioxidants & Redox Signaling. 2006; 8(7-8): 1249-52.
27) Vider J, Laaksonen D E, Kilk A, Atalay M, Lehtmaa J, Zilmer M, et al. Physical exercise induces activation of NF-κ B in human peripheral blood lymphocytes. Antioxidants and Redox Signaling. 2001; 3(6): 1131-7.
28) Oliveras-Ferraros C, Cufí S, Vazquez-Martin A, Torres-Garcia V Z, Del Barco S, Martin-Castillo B, et al. Micro (mi) RNA expression profile of breast cancer epithelial cells treated with the anti-diabetic drug metformin: induction of the tumor suppressor miRNA let-7a and suppression of the TGFβ-induced oncomiR miRNA-181a. Cell Cycle. 2011; 10(7): 1144-51.
29) Barh D, Malhotra R, Ravi B, Sindhurani P. MicroRNA let-7: An emerging next-generation cancer therapeutic. Current Oncology. 2010; 17(1): 70.
30) Simon P, Fehrenbach E, Niess A M. Regulation of immediate early gene expression by exercise: Short cuts for the adaptation of immune function. Exerc Immunol Rev. 2006; 12(1): 112-31.
31) Niu G, Wright K L, Huang M, Song L, Haura E, Turkson J, et al. Constitutive Stat3 activity up-regulates VEGF expression and tumor angiogenesis. Oncogene. 2002; 21(13): 2000-8.
32) Bollrath J, Phesse T J, von Burstin V A, Putoczki T, Bennecke M, Bateman T, et al. GP130-mediated Stat3 activation in enterocytes regulates cell survival and cell-cycle progression during colitis-associated tumorigenesis. Cancer Cell. 2009; 15(2): 91-102.
33) Paul-Pletzer K. Tocilizumab: Blockade of interleukin-6 signaling pathway as a therapeutic strategy for inflammatory disorders. Drugs Today (Barc). 2006; 42(9): 559-76.
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