4دانشیار دانشگاه تهران، دکتری تخصصی هماتولوژی و بانک خون
تاریخ دریافت: 16 شهریور 1394،
تاریخ بازنگری: 18 دی 1394،
تاریخ پذیرش: 23 دی 1394
چکیده
تمرین هوازی، رشد تومور سرطان پستان را کاهش می‌دهد. پژوهش حاضر، تغییر بیان ژن miR-15 و BcL2 و پروتئین BcL2 را به‌عنوان سازوکارهای مثبت ناشی از تمرین هوازی در سرطان پستان مورد‌بررسی قرار داده است. بدین‌منظور، 20 سر موش بالب 30 ماده (پنج تا شش هفته‌ای با میانگین تودۀ بدنی 17ـ16 گرم) با تزریق سلول‌های سرطانی MC4-L2 به سرطان مبتلا شدند. سپس، به‌صورت تصادفی به دو گروه 10 نفری تمرین و کنترل تقسیم گردیدند. در ادامه و 48 ساعت پس از آخرین جلسۀ تمرین، قربانی گشتند و نمونه‌های بافتی آن‌ها برداشته شد و در دمای 70- درجه ذخیره گردید. شایان‌ذکر است که میزان بیان miR-15 و BcL2 بافت تومور به روش ریل تایم –پی‌سی‌‌ار و میزان بیان پروتئین BcL2 با استفاده از روشالایزا اندازه‌گیری شد. نتایج نشان می‌دهد که بیان ژن و پروتئین BcL2 و نسبت رشد تومور، به‌شکل معناداری (0.001>P) در گروه تمرین در‌مقایسه با گروه کنترل کاهش یافته است و بیان miR-15 در گروه تمرین، افزایش معناداری را در‌مقایسه با گروه کنترل نشان می‌دهد (0.001>P). در‌مجموع، به‌نظر می‌رسد افزایش بیان ژن miR-15 و کاهش بیان ژن و پروتئین BcL2 ناشی از تمرین هوازی، در کاهش نسبت رشد تومور در گروه تمرین مؤثر بوده است.
1. Kruk J, Aboul-Enein H Y. Psychological stress and the risk of breast cancer: A case–control study. Cancer Detection and Prevention. 2004; 28(6): 399-408.
2. Na H K, Oliynyk S. Effects of physical activity on cancer prevention. Annals of the New York Academy of Sciences. 2011; 1229(1): 176-83.
3. Amani-Shalamzari S, Aghaalinejad H, Alizadeh S, Kazmi A, Saei M A, Minayi N, et al. The effect of endurance training on the level of tissue IL-6 and VEGF in mice with breast cancer. Journal of Shahrekord Uuniversity of Medical Sciences. 2014; 16(2): 10- 21. (In Persian).
4. Betof A S, Dewhirst M W, Jones L W. Effects and potential mechanisms of exercise training on cancer progression:A translational perspective. Brain, Behavior, and Immunity. 2013; 30(Suppl): 75-87.
5. 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.
6. Mirakhori Z, Kordi M R, Gaeini A A, Alizadeh SH, Anoosheh L, Amani S, et al. The effect of aerobic training on plasma estradiol and miR-206 and ERα expression in mice with breast cancer. Iranian Quarterly Journal of Breast Diseases. 2015; 7(4): 23-32. (In Persian).
7.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.
9. Fernandes-Silva M M, Carvalho V O, Guimarães G V, Bacal F, Bocchi E A. Physical exercise and microRNAs: New frontiers in heart failure. Arquivos Brasileiros de Cardiologia. 2012; 98(5): 459-66.
10. Rodriguez A, Griffiths-Jones S, Ashurst J L, Bradley A. Identification of mammalian microRNA host genes and transcription units. Genome Research. 2004; 14(10a): 1902-10.
11. Calin G A, Croce C M. MicroRNA signatures in human cancers. Nature Reviews Cancer. 2006; 6(11): 857-66.
12. Inui M M G, Piccolo S. MicroRNA control of signal transduction. Nat Rev Mol Cell Biol. 2010; 11(4): 252-63.
13. Chivukula R R, Mendell J T. Circular reasoning: MicroRNAs and cell-cycle control. Trends in Biochemical Sciences. 2008; 33(10): 474-81.
14. He L, Hannon G J. MicroRNAs: Small RNAs with a big role in gene regulation. Nature Reviews Genetics. 2004; 5(7): 522-31.
15. Ambros V. The functions of animal microRNAs. Nature. 2004; 431(7006): 350-5.
16. Ventura A, Jacks T. MicroRNAs and cancer: Short RNAs go a long way. Cell. 2009; 136(4): 586-91.
17. Aqeilan R, Calin G, Croce C. miR-15 a and miR-16-1 in cancer: Discovery, function and future perspectives. Cell Death & Differentiation. 2010; 17(2): 215-20.
18. Calin G A, Cimmino A, Fabbri M, Ferracin M, Wojcik S E, Shimizu M, et al. miR-15 a and miR-16-1 cluster functions in human leukemia. Proceedings of the National Academy of Sciences. 2008; 105(13): 5166-71.
19. Cimmino A, Calin G A, Fabbri M, Iorio M V, Ferracin M, Shimizu M, et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proceedings of the National Academy of Sciences of the United States of America. 2005; 102(39): 13944-9.
20. Lewis B P, Burge C B, Bartel D P. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005; 120(1): 15-20.
21. Krek A, Grün D, Poy M N, Wolf R, Rosenberg L, Epstein E J, et al. Combinatorial microRNA target predictions. Nature Genetics. 2005; 37(5): 495-500.
22. John B, Enright A J, Aravin A, Tuschl T, Sander C, Marks D S. Human microRNA targets. PLoS Biology. 2004; 2(11): 363.
23. Cory S, Adams J M. The BcL2 family: Regulators of the cellular life-or-death switch. Nature Reviews Cancer. 2002; 2(9): 647-56.
24. Sánchez-Beato M, Sánchez-Aguilera A, Piris M A. Cell cycle deregulation in B-cell lymphomas. Blood. 2003; 101(4): 1220-35.
25. Kim R, Emi M, Tanabe K, Toge T. Therapeutic potential of antisense Bcl‐2 as a chemosensitizer for cancer therapy. Cancer. 2004; 101(11): 2491-502.
26. Hoydal M A, Wisloff U, Kemi O J, Ellingsen O. Running speed and maximal oxygen uptake in rats and mice: Practical implications for exercise training. European Journal of Cardiovascular Prevention & Rehabilitation. 2007; 14(6): 753-60.
27. 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.
28. Aghaalinejad H, Tofighi A, Zahir M H, Mahdavi M, Shahrokhi S. The effect of continuous aerobic trainning on HSP70 levels in mice with breast cancer.Olampic. 2008; 16(2): 75-86. (In Persian).
29. 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.
30. 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. (In Persian).
31. 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.
32. Xia L, Zhang D, Du R, Pan Y, Zhao L, Sun S, et al. MiR‐15b and miR‐16 modulate multidrug resistance by targeting BCL2 in human gastric cancer cells. International Journal of Cancer. 2008; 123(2): 372-9.
33. Sevignani C, Calin G A, Siracusa L D, Croce C M. Mammalian microRNAs: A small world for fine-tuning gene expression. Mammalian Genome. 2006; 17(3): 189-202.
34. Calin G A, Sevignani C, Dumitru C D, Hyslop T, Noch E, Yendamuri S, et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proceedings of the National Academy of Sciences of the United States of America. 2004; 101(9): 2999-3004.
35. Chiorazzi N, Rai K R, Ferrarini M. Chronic lymphocytic leukemia. New England Journal of Medicine. 2005; 352(8): 804-15.
36. Dong J T, Boyd J C, Frierson H F. Loss of heterozygosity at 13q14 and 13q21 in high grade, high stage prostate cancer. The Prostate. 2001; 49(3): 166-71.
37. Esquela-Kerscher A, Slack F J. Oncomirs—microRNAs with a role in cancer. Nature Reviews Cancer. 2006; 6(4): 259-69.
38. Noguchi S, Mori T, Hoshino Y, Maruo K, Yamada N, Kitade Y, et al. MicroRNA-143 functions as a tumor suppressor in human bladder cancer T24 cells. Cancer Letters. 2011; 307(2): 211-20.
39. Bonci D, Coppola V, Musumeci M, Addario A, Giuffrida R, Memeo L, et al. The miR-15 a–miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nature Medicine. 2008; 14(11): 1271-7.
40. Bottoni A, Piccin D, Tagliati F, Luchin A, Zatelli M C, Degli Uberti E C. MiR‐15a and miR‐16‐1 down‐regulation in pituitary adenomas. Journal of Cellular Physiology. 2005; 204(1): 280-5.
41. Sampath D, Liu C, Vasan K, Sulda M, Puduvalli V K, Wierda W G, et al. Histone deacetylases mediate the silencing of miR-15a, miR-16, and miR-29b in chronic lymphocytic leukemia. Blood. 2012; 119(5): 1162-72.
42. Musumeci M, Coppola V, Addario A, Patrizii M, Maugeri-Sacca M, Memeo L, et al. Control of tumor and microenvironment cross-talk by miR-15 a and miR-16 in prostate cancer. Oncogene. 2011; 30(41): 4231-42.
43. Cai C K, Zhao G Y, Tian L Y, Liu L, Yan K, Ma Y L, et al. miR-15a and miR-16-1 downregulate CCND1 and induce apoptosis and cell cycle arrest in osteosarcoma. Oncology Reports. 2012; 28(5): 1764-70.
44. Diniz M G, Gomes C C, de Castro W H, Guimarães A L S, De Paula A M B, Amm H, et al. miR-15 a/16-1 influences BCL2 expression in keratocystic odontogenic tumors. Cellular Oncology. 2012; 35(4): 285-91.
45. Yang J, Cao Y, Sun J, Zhang Y. Curcumin reduces the expression of Bcl-2 by upregulating miR-15 a and miR-16 in MCF-7 cells. Medical Oncology. 2010; 27(4): 1114-8.
46. Luo Q, Li X, Li J, Kong X, Zhang J, Chen L, et al. miR-15 a is underexpressed and inhibits the cell cycle by targeting CCNE1 in breast cancer. International Journal of Oncology. 2013; 43(4): 1212-8.
47. Cittelly D M, Das P M, Salvo V A, Fonseca J P, Burow M E, Jones F E. Oncogenic HER2Δ16 suppresses miR-15 a/16 and deregulates BCL-2 to promote endocrine resistance of breast tumors. Carcinogenesis. 2010; 31(12): 2049-57.
ابتدای صفحه