Razi Journal of Medical Sciences

fa پاسخ بیان ژن PI3K و PDK در بافت کبد موش‌های مبتلا به سرطان ملانوما به یک دوره تمرینات هوازی همراه با مصرف عصاره گزنه Response of PI3K and PDK Gene Expression in Liver Tissue of Mice with Melanoma Cancer to A Course of Aerobic Exercise with Consumption of Nettle Extract فیزیولوژی ورزش Exercise Physiology پژوهشي Research <div style="text-align: justify;">زمینه و هدف: ملانوما یک تومور با منشا سلول‌های ملانین‌دار است که معمولاً در پوست آشکار می‌گردد. هدف از تحقیق حاضر بررسی پاسخ بیان ژن PI3K و  PDK در بافت کبد موش‌های مبتلا به سرطان ملانوما به یک دوره تمرینات هوازی همراه با مصرف عصاره گزنه بود. روش کار: روش تحقیق از نوع تجربی بود و در این تحقیق 20 سر موش صحرایی نر بالغ با میانگین وزن اولیه 200-250گرم  به صورت تصادفی به 4 گروه: 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 میلی گرم/کیلوگرم/روز عصاره اتانولی گیاه گزنه را به روش خوراکی و به مدت 8 هفته مصرف کردند. برای اندازه گیری میزان بیان ژن PI3K و  PDK از روشRT  PCR استفاده شد. برای بررسی تغییرات در هریک از متغیرهای تحقیق از روش آنالیز واریانس یکطرفه و در صورت معنی داری آماری از آزمون تعقیبی توکی  استفاده گردید. یافته‌ها: تجزیه و تحلیل دادهها نشان داد بیان ژن PI3K و PDK در گروه های تجربی نسبت به گروه کنترل کاهش معناداری داشت (04/0p=). همچنین بیان ژن PDK در گروه ترکیبی نسبت به گروه کنترل کاهش معناداری داشت (000/0p=). نتیجه‌گیری: نتایج نشان می دهد که مصرف عصاره گزنه همراه با تمرینات هوازی از طریق کاهش بیشتر سطوح PI3K در گروه ترکیبی، احتمال دارد از طریق غیرفعال کردن مسیر PI3K/AKT/mTOR/S6K1 نقش موثری در القاء آپوپتوز در سلول‌های سرطانی داشته است.</div> <div style="text-align: justify;"> Background & Aims: Melanoma is a tumor originating from melanin cells that usually appears in the body skin. The most common risk factor or trigger for almost all types of skin cancer is exposure to ultraviolet (UV) radiation, which can damage DNA in skin cells. Aberrant signaling in PI3K/AKT/mTOR is also observed in pathological skin. PI3K signaling is primarily activated in epidermal compartments, particularly in keratinocytes, following their exposure to environmental factors. The biological activities of nettle are important due to their ability to induce or inhibit key processes in cellular metabolism and their ability to activate apoptosis pathways. Nettle plants contain antioxidant phenolic compounds that may play an important role in cancer prevention. In a study, the antiproliferative effect of nettle root extract on human prostate cancer cells was demonstrated. This study was conducted considering the role of regular physical activity in promoting the health of body tissues, improving defense mechanisms, and creating or inhibiting key processes in cellular metabolism and the ability to activate related signaling pathways.The aim of this study was to investigate the response of PI3K and PDK gene expression in liver tissue of mice with melanoma to a period of aerobic exercise with nettle extract. Methods: The research method was experimental. In this study, 20 adult male rats with an average initial weight of 200-250 grams were randomly divided into 4 groups: control, exercise, extract and exercise + extract. The training program consisted of 30 minutes of running on a treadmill without a slope at a speed of 16 meters per minute for the first week, and one meter per minute was added every week until it reached 22 meters per minute in the eighth week. A portion of the nettle plant stem and leaves were collected and washed after cutting into small pieces, then dried in the open air and ground into powder using a machine. Then the nettle plant powder was placed in a container, 2 liters of distilled water was added to it and the beaker was placed on a special heater with gentle heat. After boiling, the desired decoction was filtered with filter paper. The extraction was placed inside a distillation machine under vacuum. One week after melanoma induction, the experimental group consumed 30 mg/kg / day of nettle ethanolic extract orally for 8 weeks. RT PCR was used to measure the expression of PI3K and PDK genes. One-way analysis of variance was used to examine the changes of each research variable and if statistically significant, Tukey's post hoc test was used. Results: Data analysis showed that eight weeks of nettle extract consumption and aerobic exercise had an effect on PI3K levels in mice with melanoma cancer in different groups. Also, using post hoc tests, the difference in the level of PI3K gene expression changes among different groups was significant compared to the control group.Data analysis showed that PI3K and PDK gene expression was significantly reduced in the experimental groups compared to the control group (p = 0.04). Data analysis also showed that eight weeks of nettle extract consumption and aerobic exercise had an effect on PDK levels in mice with melanoma cancer in different groups. Also, using Tukey's post hoc test, the difference in the level of PDK gene expression changes among different groups was significant compared to the control group. PDK gene expression was significantly reduced in the combination group compared to the control group (p = 0.000). Conclusion: The results of the present study showed that consumption of nettle extract and aerobic exercise significantly reduced PI3K and PDK levels in the experimental groups compared to the control group. Phosphatidylinositol 3-kinase represents a family of kinases that play a vital role in mammalian cells by regulating proliferation, growth, and survival. Dysregulation of PI3K-dependent signaling, and in particular the PI3K/AKT pathway, has been implicated in the mammalian target of rapamycin (mTOR) pathway in various pathological conditions. In patients with skin cancer, treatment with an mTORC1 inhibitor results in partial or complete tumor arrest. Several reports suggest that the PI3K/AKT/mTOR/S6K1 pathway can be activated in skin cancers by UV exposure. Emerging evidence suggests that nettle extract is biologically active and has the ability to protect against oxidative stress, malignancies, and angiogenesis. The anticancer properties of nettle stem from its ability to inhibit the PI3K/AKT signaling pathway, reduce glucose uptake and metabolism, initiate apoptosis and autophagy, and regulate microRNA expression.  The results show that consumption of nettle extract along with aerobic exercise by further reducing PI3K levels in the combination group, may have effective role in inducing apoptosis in cancer cells by inactivating the PI3K/AKT/mTOR /S6K1 pathway. </div> عصاره گزنه, آپوپتوز, مسیر سیگنالی, سرطان ملانوما Nettle extract, Apoptosis, Signal pathway, Melanoma cancer 1 11 http://rjms.iums.ac.ir/browse.php?a_code=A-10-2398-7&slc_lang=fa&sid=1 Seyyede Fateme Motavalli سیده فاطمه متولی 3900319475328460087842 3900319475328460087842 No PhD Student, Department of Sport Physiology, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran دانشجوی دکتری، گروه فیزیولوژی ورزشی، واحد آیت الله آملی، دانشگاه آزاد اسلامی، آمل، ایران Alireza Barari علیرضا براری Alireza54.barari@gmail.com 3900319475328460087843 0001-0001-5199-463X Yes Associate Professor, Department of Sport Physiology, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran دانشیار، گروه فیزیولوژی ورزشی، واحد آیت الله آملی، دانشگاه آزاد اسلامی، آمل، ایران Ahmad Abdi احمد عبدی 3900319475328460087844 3900319475328460087844 No Associate Professor, Department of Sport Physiology, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran دانشیار، گروه فیزیولوژی ورزشی، واحد آیت الله آملی، دانشگاه آزاد اسلامی، آمل، ایران Hosein Abed Natanzi حسین عابد نطنزی 3900319475328460087845 3900319475328460087845 No Assistant Professor, Department of Sport Physiology, Science and Research Branch, Islamic Azad University, Tehran, Iran استادیار، گروه فیزیولوژی ورزشی، واحد علوم و تحقیقات، دانشگاه آزاد اسلامی، تهران، ایران