تاثیر تمرینات استقامتی و مصرف عصاره گزنه بر بیان ژن BCL-2و TNF-αدر موش های مبتلا به سرطان ملانوما
محورهای موضوعی : مجله پلاسما و نشانگرهای زیستیلیلا موسوی 1 , علیرضا براری 2 , اسیه عباسی دلویی 3 , حسین عابد نطنزی 4
1 - دانشجوی دکتری فیزیولوژی ورزشی،گروه فیزیولوژی ورزشی، واحد آیت الله آملی، دانشگاه آزاد اسلامی، آمل.ایران.
2 - گروه فیزیولوژی ورزشی, واحد آیت الله آملی, دانشگاه آزاد اسلامی , آمل
3 - دانشیار، گروه فیزیولوژی ورزشی، واحد آیت الله آملی، دانشگاه آزاد اسلامی، آمل.
4 - استادیار،گروه فیزیولوژی ورزشی، واحد علوم و تحقیقات، دانشگاه آزاد اسلامی، تهران.ایران.
کلید واژه: سرطان ملانوما, عصاره گزنه, آپوپتوز, TNF-α, Bcl-2,
چکیده مقاله :
زمینه و هدف: ملانوما وخیم ترین نوع سرطان پوست است که از سلول های رنگدانه ای ملانین تشکیل شده است. هدف از تحقیق حاضر بررسی تاثیر تمرینات استقامتی و مصرف گزنه بر بیان ژن BCL-2و TNF-αدر موش های مبتلا به سرطان ملانوما بود.روش کار: آزمودنی ها شامل موش های صحرایی نر ویستار بودند که پس از سازگاری دو هفته ای به صورت تصادفی به 4 گروه شامل گروه های: کنترل، تمرین، عصاره و تمرین+عصاره تقسیم شدند. برنامه تمرین شامل 30 دقیقه دویدن روی تردمیل بدون شیب و با سرعت 16 متر در دقیقه برای هفته اول بود و هر هفته یک متر بر دقیقه اضافه شد تا در هفته هشتم به 22 متر بر دقیقه رسید. یک هفته پس از القا سرطان ملانوما، گروه تجربی میزان 30 mg/kg/dayعصاره اتانولی گیاه گزنه را به روش خوراکی و به مدت 8 هفته مصرف کردند.برای اندازه گیری میزان بیان ژن از RT PCR استفاده شد.یافتهها: تجزیه و تحلیل داده ها نشان داد که مصرف عصاره گزنه و تمرینات استقامتی بر سطح بیان ژنBCL-2 و TNF-αدر موش های مبتلا به سرطان ملانوما در گروه های مختلف کاهش معناداری دارد(به ترتیب p=0.000 ,p=0.025). هم چنین نتایج نشان داد که تفاوت سطح تغییرات بیان ژنBCL-2 و TNF-αبین گروه تمرین+عصاره با گروه کنترل(به ترتیب p=0.002 ,p=0.014)کاهش معناداری داشت.نتیجه گیری: فعالیت بدنی منظم همراه با مصرف عصاره گزنه احتمالاً می تواند از طریق کاهش عوامل التهابی منجر به کاهش عوامل ضد آپوپتوزی و ایجاد آپوپتوز در سلول های سرطانی شود.
Inroduction & Objective: : Melanoma is the most serious type of skin cancer, which is made up of melanin pigment cells.The aim of this study was to evaluate the effect of endurance training and nettle consumption on BCL-2 and TNF-α gene expression in mice with melanoma.Material and Methods: The subjects included male Wistar rats that after two weeks of adjustment were randomly divided into 4 groups including: control, exercise, extract and exercise + extract. Exercise program included 30 minute of running on a treadmill was steep and at a speed of 16 meters per minute for the first week, and every week one meter per minute was added until the eighth week it reached 22 meters per minute. One week after melanoma induction, the experimental group consumed 30 mg / kg / day of nettle ethanol extract orally for 8 weeks. RT PCR was used to measure gene expression.Results: Data analysis showed that consumption of nettle extract and endurance training significantly reduced the expression level of BCL-2 and TNF-α genes in mice with melanoma in different groups (p = 0.000, p = 0.025, respectively). The results also showed that the difference in the level of changes in BCL-2 and TNF-α gene expression between the exercise and extract group with the control group (p = 0.002, p = 0.014, respectively) was significantly reduced.Conclusion: Regular physical activity combined with consumption of nettle extract can probably reduce anti-apoptotic factors and cause apoptosis in cancer cells by reducing inflammatory factors.
2.Amani Shalamzari, S., Agha-Alinejad, H., Alizadeh, Sh., Shahbazi, Sh., Kashani Khatib, Z., Kazemi, A. (2014). 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, 17(4); 231-58.
3.Amjadi, F., Javanmard, SH., Zarkesh-Esfahani, H., Khazaei, M., Narimani, M. (2011). Leptin promotes melanoma tumor growth in mice related to increasing circulating endothelial progenitor cells numbers and plasma NO production. J Exp Clin Cancer Res, 30; 21.
4.Campbell, K., Tiernan, A., Li, SS., Sorensen, BE., Yasui, Y., Lampe, JW. (2007). Effect of a 12- month exercise intervention on the apoptotic regulating proteins bax and Bcl-2 in colon crypts: A randomized controlled trial. Cancer Epidemiol. Biomarkers Prev, 16(9); 1767-74.
5.Childs, AC., Phaneuf, SL., Dirks, AJ., Phillips, T., Leeuwenburgh, C. (2002). Doxorubicin treatment in vivo causes cytochrome C release and cardiomyocyte apoptosis, as well as increased mitochondrial efficiency, superoxide dismutase activity, and Bcl-2:Bax ratio. Cancer Research, 62(16); 4592-4598.
6.Cory, S., Adams, J.M. (2002). The BcL2 family: Regulators of the cellular life-or-death switch. Nature Reviews Cancer, 2(9); 647-56.
7.Debatin, KM. (1997). Cytotoxic drugs, programmed cell death, and the immune system: defining new roles in an old play. Journal of the National Cancer Institute, 89(11); 750-751
8.Eliassen, AH., Hankinson, SE., Rosner, B., Holmes, MD., Willett, WC. (2010). Physical activity and risk of breast cancer among postmenopausal women. Arch Intern Med, 170(19); 1758-64.
9.Fesik, SW., Shi, Y. (2001). Structural biology. Controlling the caspases. Science, 294(5546); 1477-1478.
10.Finn, GJ., Creaven, BS., Egan, DA. (2004). A study of the role of cell cycle events mediating the action of comarian derivatives in human malignant melanoma cells. Cancer Letters, 214; 43-54.
11.Foo, JB., Yazan, LS., Tor, YS., Wibowo, A., Ismail, N., How, CW. (2015). Induction of cell cycle arrest and apoptosis by betulinic acid-rich fraction from Dillenia suffruticosa root in MCF-7 cells involved p53/p21 and mitochondrial signalling pathway. J Ethnopharmacol,166; 270-8.
12.Jafari, A., Pourrazi, H., Nikookheslat, S., Baradaran, B. (2015). Effect of exercise training on Bcl-2 and bax gene expression in the rat heart. Gene Cell Tissue, 2;4.
13.Konrad, L., Müller, H-H., Lenz, C., Laubinger, H., Aumüller, G., Lichius, JJ. (2000). Antiproliferative effect on human prostate cancer cells by a stinging nettle root (Urtica dioica) extract. Planta Med, 66(1); 44-7.
14.Kumar, V., Abbas, A., Aster, J. (2014). Robbins Pathologic Basis of Disease. 9th ed Tehran, Iran: Arjomand.
15.Lahmann, PH., Hoffmann, K., Allen, N., Van Gils, CH., Khaw, KT., Tehard, B. (2004). Body size and breast cancer risk: findings from the european prospective investigation into cancer and nutrition (EPIC). International Journal of Cancer, 111(5); 762-71.
16.Lee, S. D., Shyu, W. C., Cheng, I. S., Kuo, C. H., Chan, Y. S., Lin, Y. M. (2013). Effects of exercise training on cardiac apoptosis in obese rats. Nutrition, metabolism, and cardiovascular diseases. NMCD, 23(6); 566–573. https://doi.org/10.1016/j.numecd.2011.11.002.
17.Leite, V.C., Santos, RF., Chen, LC., Guillo, LA. (2004). Psoralen derivatives and longwave ultraviolet irradiation are active in vitro against human melanoma cell line. J Photochemistry and Photobiology, B; Biology, 76; 49-53.
18.Leung, LK., Wang, TT. (1999). Differential effects of chemotherapeutic agents on the Bcl-2/Bax apoptosis pathway in human breast cancer cell line MCF-7. Breast Cancer Research And Treatment, 55(1); 73-83.
19.Mantovani, G., Macciò, A., Mura, L. (2000). Serumlevels of leptin and proinflammatory cytokines in patients with advanced-stage cancer at differentsites. J Mol Med (Berl), 78; 554-61.
20.McIlwain, DR., Berger, T., Mak, TW. (2013). Caspase functions in cell death and disease. Cold Spring Harb Perspect Biol, 5(4); a008656.
21.Mirakhori, Z., Kordi, M., Alizadeh, SH., Gaieni, AA. The investigation of the preventive and therapeutic therapy assistance on the growth rate of the tumor, E2 and expression of 206-miR and ERα tumor tissue of breast cancer. Journal of Applied exercise Physiology, 11; 87-98.
22.Mousavi, S. M., Gouya, M. M., Ramazani, R., Davanlou, M., Hajsadeghi, N., Seddighi, Z. (2009). Cancer incidence and mortality in Iran. Annals of oncology: official journal of the European Society for Medical Oncology, 20(3); 556–563. https://doi.org/10.1093/annonc/mdn642
23.Moller, P., Wallin, H., Knudsen, LE. (1996). Oxidative stress associated with exercise, psychological stress and life-style factors. Chemico-Biological Interactions, 102(1); 17-36.
24.Mohammadi Gorji, S., Karimpour Malekshah, AA. (2013). Effect of doxorubicin on Bcl2 and Bax expression in rat heart. Journal of Gorgan University of Medical Sciences, 15(1); 19-24. [Persian].
25.Nahata, A., Dixit, V. (2012). Ameliorative effects of stinging nettle (Urtica dioica) on testosterone‐induced prostatic hyperplasia in rats. Andrologia, 44(s1); 396-409.
26.Namiki, M. (1990). Antioxidants/ antimutagens in food. Critical Reviews in Food Science & Nutrition, 29(4); 273-300.
27.Obertreis, B., Giller, K., Teucher, T., Behnke, B., & Schmitz, H. (1996). Antiphlogistische effekte von extractum urticae dioicae foliorum im vergleich zu kaffeoyläpfelsäure [anti-inflammatory effect of Urtica dioica folia extract in comparison to caffeic malic acid]. Arzneimittel-Forschung, 46(1); 52–56.
28.Otles, S., Yalcin, B. (2012). Phenolic compounds analysis of root, stalk, and leaves of nettle. The Scientific World Journal, 564367. https://doi.org/10.1100/2012/564367
29.Pal, SK., Shukla, Y. (2003). Herbal medicine: current status and the future. APJCP, 4(4); 281-8.
30.Shailajan, S., Hande, H., Singh, D., Tiwari, B. (2014). Estimation of ursolic acid from Urtica dioica L. using validated HPTLC method. Journal of Applied Pharmaceutical Science, 4; 092-095.
31.Siegel, RL., Miller, KD, Jemal, A. (2018). Cancer statistics. CA: A Cancer Journal for Clinicians, 68(1); 7-30.
32.Sharifi, S., Barar, J., Hejazi, MS., Samadi, N. (2015). Doxorubicin changes Bax /Bcl-xL ratio, caspase-8 and 9 in breast cancer cells. Advanced Pharmaceutical Bulletin, 5(3);351-359.
33.Smeltzer, SC., Bare, BG., Hinkle, JL., Cheever, KH. (2010). Brunner and Suddarth’s Textbook of Medical Surgical Nursing. 12th ed London, England: Wolters Kluwer, 205–231.
34.Vainshtein, A., Kazak, L., Hood, DA. (2011). Effects of endurance training on apoptotic susceptibility in striatedmuscle. J Appl Physiol, 110(6); 1638-1645.
35.Würstle, ML., Laussmann, MA., Rehm, M. (2012). The central role of initiator caspase-9 in apoptosis signal transduction and the regulation of its activation and activity on the apoptosome. Exp Cell Res, 318(11); 1213-1220.
36.Yan, D., Qin, N., Zhang, H. (2009). Expression of TNF-α leader sequence renders MCF-7 tumor cells resistant to the cytotoxicity of soluble TNF-α. Breast Cancer Res Treat, 116; 91-102.
37.Yvonne, M. (2008). Coyle physical activity as a negative modulator of estrogen-induced breast cancer. Cancer Causes Control, 19;1021- 9.
_||_