اثر یک دوره‌ی تمرینات بدنی بر مقادیر پلاسمایی و بیان ژن Hypoxia-Inducible Factor-1 (HIF-1) و سطح سرمی آنتی‌ژن اختصاصی پروستات در مردان مبتلا به سرطان پروستات

نوع مقاله : مقاله های پژوهشی

نویسندگان

1 دانشجوی دکتری، گروه فیزیولوژی ورزشی، دانشکده‌ی تربیت بدنی، واحد آیت‌اله آملی، دانشگاه آزاد اسلامی، آمل، ایران

2 دانشیار ،گروه فیزیولوژی ورزشی، دانشکده‌ی تربیت بدنی، واحد آیت‌اله آملی، دانشگاه آزاد اسلامی، آمل، ایران

3 استادیار، گروه فیزیولوژی ورزشی، دانشکده‌ی تربیت بدنی، واحد آیت‌اله آملی، دانشگاه آزاد اسلامی، آمل، ایران

4 دکتری پزشکی مولکولی،گروه پاتولوژی، آزمایشگاه ژنتیک مولکولی، بیمارستان فوق تخصصی بقیه‌اله الاعظم (عج)، تهران، ایران

چکیده

مقدمه: تمرینات بدنی، از راه تعدیل آنژیوژنز در بافت تومور نقش حمایتی را در درمان سرطان پروستات ایفا می‌کنند. عامل القا شونده به وسیله‌ی هیپوکسی 1 (Hypoxia-inducible factor-1 یا HIF-1)، نقش مهمی در روند آنژیوژنز و رشد تومور دارد. آنتی‌ژن اختصاصی پروستات (Prostate-specific antigen یا PSA)، قابل دسترس‌ترین نشانگر تومور برای تشخیص سریع سرطان پروستات است. هدف از انجام پژوهش حاضر، بررسی اثر تمرینات بدنی بر مقادیر پلاسمایی و بیان ژن HIF-1 و سطح سرمی PSA مردان مبتلا به سرطان پروستات بود.روش‌ها: در این مطالعه‌ی کارآزمایی بالینی، با مراجعه به بخش پاتولوژی بیمارستان فوق تخصصی بقیه‌اله الاعظم (عج) تهران و بررسی مدارک پزشکی مردان مبتلا به سرطان پروستات در 6 ماه اول سال 1395، تعداد 20 مرد مبتلا به سرطان پروستات به طور تصادفی انتخاب و به دو گروه مساوی مورد (با سن 04/10 ± 7/63 سال، وزن 26/11 ± 00/78 کیلوگرم و شاخص توده‌ی بدنی 44/2 ± 27/28 کیلوگرم/مترمربع) و شاهد (با سن 69/4 ± 5/61 سال، وزن 26/11 ± 20/79 کیلوگرم و شاخص توده‌ی بدنی 83/2 ± 93/27 کیلوگرم/مترمربع) تقسیم شدند. گروه مورد، به مدت 8 هفته و هر هفته 3 جلسه‌ی60 دقیقه‌ای، تمرین ترکیبی مقاومتی و استقامتی در زمان برابر با شدت 75-60 درصد یک تکرار بیشینه و 75-60 درصد بیشینه‌ی ضربان قلب انجام دادند. گروه شاهد، هیچ مداخله‌ای دریافت نکردند. نمونه‌ های خونی جهت بررسی PSA و HIF-1 به روش Enzyme-linked immunosorbent assay (ELISA) و Real-time polymerase chain reaction (Real-time PCR) و با آزمون آماری Dependent t و Independent t سنجیده شد.یافته‌ها: تمرین ترکیبی، سبب کاهش معنی‌دار مقادیر پلاسمایی (007/0 = P) و بیان ژن HIF-1 (005/0 = P) و سطح سرمی PSA (005/0 = P) در گروه مورد شد.نتیجه‌گیری: با توجه به اهمیت PSA در تشخیص سرطان پروستات و نقش HIF-1 در آنژیوژنز تومور، تمرین ترکیبی می‌تواند از راه تعدیل HIF-1 و PSA، نقش مؤثری در کاهش روند پیشرفت سرطان پروستات داشته باشد.

کلیدواژه‌ها


عنوان مقاله [English]

The Effect of a Period of Physical Exercise on the Plasma and Gene Expression Levels of Hypoxia-Inducible Factor-1 (HIF-1) and Serum Prostate Specific Antigen Levels in Men with Prostate Cancer

نویسندگان [English]

  • Marzieh Beigom Hejazian 1
  • Alireza Barari 2
  • Asieh Abbasi-Daloii 3
  • Kambiz Hasrak 4
1 PhD Student, Department of Exercise Physiology, School of Physical Education, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran
2 Associate Professor, Department of Exercise Physiology, School of Physical Education, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran
3 Assistant Professor, Department of Exercise Physiology, School of Physical Education, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran
4 PhD in Molecular Medicine, Department of Pathology, Molecular Genetics Laboratory, Baqiyatallah al-Azam Subspecialty Hospital, Tehran, Iran
چکیده [English]

Background: Physical exercises play a supportive role in the treatment of prostate cancer by modulating angiogenesis in tumor tissue. The hypoxia-inducible factor-1 (HIF-1) modulates angiogenesis and tumor growth. Prostate specific antigen (PSA) is the most widely available tumor marker for the rapid diagnosis of prostate cancer. The purpose of this study was to investigate the effect of physical exercises in the expression of HIF-1 gene levels in plasma, and the PSA level in the sera of men with prostate cancer.Methods: In this clinical trial study, 20 men with prostate cancer were randomly selected from the pathology department of Baqiyatallah al-Azam subspecialty hospital in Tehran, Iran, during the middle 6 months of 2016. Patients were divided into two groups of experimental [age: 63 ± 10 years, weight: 78 ± 11 kg, body mass index (BMI): 28.5 ± 2.4 kg/m2] and control [age = 62 ± 4 years, weight: 79 ± 11 kg, BMI: 27.9 ± 2.9 kg/m2). The experimental group performed 8 weeks of 60 minutes per session training including 3 sessions per week. The workouts were the combination of exercises with resistance and endurance training per session as 60-75 percent of one repetition maximum, and 60-75 percent of maximum heart rate. The control group did not receive any intervention. Blood samples were tested for PSA and HIF-1 using enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR) methods, respectively, and the data were analyzed using dependent and independent t test.Findings: Combined exercise significantly decreased the plasma level (P = 0.007) and gene expression (P = 0.005) of HIF-1, as well as serum PSA level (P = 0.005) in the experimental group compared with control group.Conclusion: Considering the importance of PSA in the diagnosis of prostate cancer, and the role of HIF-1 in tumor angiogenesis, the combined exercise can be effective in reducing the progression of prostate cancer by modifying HIF-1 and PSA.

کلیدواژه‌ها [English]

  • Prostate-specific antigen
  • Physical Activity
  • Prostatic cancer
  • Hypoxia-inducible factor
  1. Nodouzi V, Nowroozi M, Hashemi M, Javadi G, Mahdian R. Concurrent Down-regulation of pten and nkx3.1 expression in iranian patients with prostate cancer. Int Braz J Urol 2015; 41(5): 898-905.
  2. Taghavi R, Ameli M, Mahdavi R, Shakiba B, Gholami Mahtaj L. Relationship between body mass index and prostate specific antigen in patient with lower urinary tract symptoms. Razi J Med Sci 2013; 20(113): 87-91. [In Persian].
  3. Baghinia M R, Shariatzadeh S M, Baghinia N. Evaluation of calcium as a tumor-marker in prostate cancer. J Arak Uni Med Sci 2014; 16(10): 19-26. [In Persian].
  4. Hutterer G, Perrotte P, Gallina A, Walz J, Jeldres C, Traumann M, et al. Body mass index does not predict prostate-specific antigen or percent free prostate-specific antigen in men undergoing prostate cancer screening. Eur J Cancer 2007; 43(7): 1180-7.
  5. Fathollahi Shoorabeh F, Dabidiroshan V, Sheikh Saraf B, Nuri R. Investigating the effects of regular resistance training and prostatic massage on proinflammatory markers and serum prostate-specific antigen levels in males with prostate cancer. Middle East J Rehabil Health 2016; 3(1): e33651.
  6. Oremek GM, Seiffert UB. Physical activity releases prostate-specific antigen (PSA) from the prostate gland into blood and increases serum PSA concentrations. Clin Chem 1996; 42(5): 691-5.
  7. Luboldt HJ, Peck KD, Oberpenning F, Schmid HP, Semjonow A. Bicycle riding has no important impact on total and free prostate-specific antigen serum levels in older men. Urology 2003; 61(6): 1177-80.
  8. Kimbro KS, Simons JW. Hypoxia-inducible factor-1 in human breast and prostate cancer. Endocr Relat Cancer 2006; 13(3): 739-49.
  9. Fathollahi Shoorabeh F L, Faramarzi M, Hemmati R L, Nuri R. The effects of ten weeks resistance training on resting levels of some angiogenesis factors among men with prostate cancer. Yafte 2017; 19(4): 129-39. [In Persian].
  10. Masoud GN, Li W. HIF-1alpha pathway: Role, regulation and intervention for cancer therapy. Acta Pharm Sin B 2015; 5(5): 378-89.
  11. Brown JC, Winters-Stone K, Lee A, Schmitz KH. Cancer, physical activity, and exercise. Compr Physiol 2012; 2(4): 2775-809.
  12. Zielinski MR, Muenchow M, Wallig MA, Horn PL, Woods JA. Exercise delays allogeneic tumor growth and reduces intratumoral inflammation and vascularization. J Appl Physiol (1985) 2004; 96(6): 2249-56.
  13. McCullough DJ, Nguyen LM, Siemann DW, Behnke BJ. Effects of exercise training on tumor hypoxia and vascular function in the rodent preclinical orthotopic prostate cancer model. J Appl Physiol (1985) 2013; 115(12): 1846-54.
  14. Galvao DA, Nosaka K, Taaffe DR, Peake J, Spry N, Suzuki K, et al. Endocrine and immune responses to resistance training in prostate cancer patients. Prostate Cancer Prostatic Dis 2008; 11(2): 160-5.
  15. Nelson ME, Rejeski WJ, Blair SN, Duncan PW, Judge JO, King AC, et al. Physical activity and public health in older adults: recommendation from the American College of Sports Medicine and the American Heart Association. Circulation 2007; 116(9): 1094-105.
  16. Santa MD, Alibhai S MH, Matthew AG, Guglietti CL, Pirbaglou M, Trachtenberg J, et al. A randomized trial of aerobic versus resistance exercise in prostate cancer survivors. J Aging Phys Act 2013; 21(4): 455-78.
  17. Edge SB, Compton CC. The American Joint Committee on Cancer: The 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 2010; 17(6): 1471-4.
  18. Coburn JW, Malek MH. NSCA's essentials of personal training. 2nd ed. Champaign, IL: Human Kinetics; 2012.
  19. Zhong H, De Marzo AM, Laughner E, Lim M, Hilton DA, Zagzag D, et al. Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases. Cancer Res 1999; 59(22): 5830-5.
  20. Bos R, van der Groep P, Greijer AE, Shvarts A, Meijer S, Pinedo HM, et al. Levels of hypoxia-inducible factor-1alpha independently predict prognosis in patients with lymph node negative breast carcinoma. Cancer 2003; 97(6): 1573-81.
  21. Betof AS, Dewhirst MW, Jones LW. Effects and potential mechanisms of exercise training on cancer progression: a translational perspective. Brain Behav Immun 2013; 30 Suppl: S75-S87.
  22. Shalamzari SA, Agha-Alinejad H, Alizadeh S, Shahbazi S, Khatib ZK, 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. Iran J Basic Med Sci 2014; 17(4): 231-58.
  23. Zhu ML, Kyprianou N. Androgen receptor and growth factor signaling cross-talk in prostate cancer cells. Endocr Relat Cancer 2008; 15(4): 841-9.
  24. Jackson MW, Roberts JS, Heckford SE, Ricciardelli C, Stahl J, Choong C, et al. A potential autocrine role for vascular endothelial growth factor in prostate cancer. Cancer Res 2002; 62(3): 854-9.
  25. Baeriswyl V, Christofori G. The angiogenic switch in carcinogenesis. Semin Cancer Biol 2009; 19(5): 329-37.
  26. Culos-Reed SN, Robinson JW, Lau H, Stephenson L, Keats M, Norris S, et al. Physical activity for men receiving androgen deprivation therapy for prostate cancer: Benefits from a 16-week intervention. Support Care Cancer 2010; 18(5): 591-9.
  27. Segal RJ, Reid RD, Courneya KS, Malone SC, Parliament MB, Scott CG, et al. Resistance exercise in men receiving androgen deprivation therapy for prostate cancer. J Clin Oncol 2003; 21(9): 1653-9.
  28. Galvao DA, Nosaka K, Taaffe DR, Spry N, Kristjanson LJ, McGuigan MR, et al. Resistance training and reduction of treatment side effects in prostate cancer patients. Med Sci Sports Exerc 2006; 38(12): 2045-52.
  29. Brown JK, Byers T, Doyle C, Coumeya KS, Demark-Wahnefried W, Kushi LH, et al. Nutrition and physical activity during and after cancer treatment: an American Cancer Society guide for informed choices. CA Cancer J Clin 2003; 53(5): 268-91.
  30. Mardanpour-Shahrekordi Z, Banitalebi E, Faramarzi M, Bagheri L, Mardanpour-Shahrekordi E. The effect of sequence order of combined training (resistance and endurance) on strength, aerobic capacity and body composition in older women: a randomized clinical trial. J Shahrekord Univ Med Sci 2015; 17(3): 1-12. [In Persian].