fa بررسی اثر ضد توموری استیگماسترول بر بیان ژنهای MCL-1 و BCL-XL در مدلهای حیوانی سرطان پستان بیوشیمی Biochemistry پژوهشی Original <span style="font-size:11pt"><span style="line-height:normal"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:Calibri,sans-serif"><b><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">سابقه و هدف: </span></span></b><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">سرطان پستان به عنوان شایع</span></span><span dir="LTR" style="font-size:9.0pt">‌</span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">ترین نوع سرطان در زنان است. یکی از عوامل مرگ</span></span><span dir="LTR" style="font-size:9.0pt">‌</span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">و</span></span><span dir="LTR" style="font-size:9.0pt">‌</span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">میر ناشی از سرطان افزایش فعالیت ضدآپوپتوزی سلول</span></span><span dir="LTR" style="font-size:9.0pt">‌</span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">های سرطانی است. فیتوسترول</span></span><span dir="LTR" style="font-size:9.0pt">‌</span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">ها گروهی از ترکیب‌های طبیعی هستند که از طریق مکانیسم</span></span><span dir="LTR" style="font-size:9.0pt">‌</span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">های مختلفی سبب مهار رشد انواع سلول</span></span><span dir="LTR" style="font-size:9.0pt">‌</span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">های سرطانی می</span></span><span dir="LTR" style="font-size:9.0pt">‌</span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">شوند. استیگماسترول به عنوان یکی از ترکیب‌های گروه فیتواسترول</span></span><span dir="LTR" style="font-size:9.0pt">‌</span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">ها دارای</span></span><span dir="LTR" style="font-size:9.0pt">‌</span><span style="font-size:10.0pt"><span b="" nazanin="" style="font-family:"> آثار ضدسرطانی است. در این تحقیق اثر ضد توموری استیگماسترول بر بیان ژن</span></span><span dir="LTR" style="font-size:9.0pt">‌</span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">های</span></span><span dir="LTR" style="font-size:9.0pt"><span new="" roman="" style="font-family:" times=""> MCL-1 </span></span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">و</span></span><span dir="LTR" style="font-size:9.0pt"><span new="" roman="" style="font-family:" times=""> BCL-XL </span></span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">در مدل</span></span><span dir="LTR" style="font-size:9.0pt">‌</span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">های حیوانی سرطان سینه بررسی ‌شد.</span></span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:Calibri,sans-serif"><b><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">روش کار:</span></span></b><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:"> در این مطالعه تجربی، 15سر موش</span></span> <span dir="LTR" style="font-size:9.0pt"><span new="" roman="" style="font-family:" times="">BALB/C </span></span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">در سه گروه با تومور پستان به صورت زیرپوستی پیوند زده شدند. به گروه اول دوز6 میلی</span></span><span dir="LTR" style="font-size:9.0pt">‌</span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">گرم بر کیلوگرم استیگماسترول و گروه دوم 20 میلی</span></span><span dir="LTR" style="font-size:9.0pt">‌</span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">گرم بر کیلوگرم سیکلوفسفامید و گروه سوم (کنترل) محلول اتانول رقیق</span></span><span dir="LTR" style="font-size:9.0pt">‌</span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">شده با</span></span><span dir="LTR" style="font-size:9.0pt"><span new="" roman="" style="font-family:" times=""> PBS(1:2) </span></span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">به صورت داخل صفاقی</span></span><span dir="LTR" style="font-size:9.0pt"><span new="" roman="" style="font-family:" times=""> (IP) </span></span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">تیمار شدند. حجم تومور به مدت 10 روز توسط کولیس</span></span><span dir="LTR" style="font-size:9.0pt">‌</span><span lang="FA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">ورنیه </span></span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">دیجیتال اندازه</span></span><span dir="LTR" style="font-size:9.0pt">‌</span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">گیری شد. سپس موش‌ها کشته و بافت تومور آنها برای انجام و تغییرهای بیان ژن</span></span><span dir="LTR" style="font-size:9.0pt">‌</span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">های </span></span><span dir="LTR" style="font-size:9.0pt"><span new="" roman="" style="font-family:" times="">MCL-1</span></span><span lang="FA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:"> و </span></span><span dir="LTR" style="font-size:9.0pt"><span new="" roman="" style="font-family:" times="">BCL-XL</span></span><span lang="FA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:"> با </span></span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">روش </span></span><span dir="LTR" style="font-size:9.0pt"><span new="" roman="" style="font-family:" times="">(Real-time PCR)</span></span><span style="font-size:10.0pt"><span b="" nazanin="" style="font-family:"> بررسی شد.</span></span><span dir="LTR" style="font-size:9.0pt"><span style="font-family:"Times New Roman",serif"></span></span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:Calibri,sans-serif"><b><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">یافته</span></span></b><b><span dir="LTR" style="font-size:9.0pt">‌</span></b><b><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">ها:</span></span></b><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:"> طبق نتایج به</span></span><span dir="LTR" style="font-size:9.0pt">‌</span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">دست‌آمده، تیمار موش‌های توموری با استیگماسترول در مقایسه با گروه کنترل، رشد تومور را مهار می‌کند. همچنین تیمار موش‌های توموری با استیگماسترول سبب کاهش بیان ژن</span></span><span dir="LTR" style="font-size:9.0pt">‌</span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">های ضد آپوپتوزی</span></span><span dir="LTR" style="font-size:9.0pt"><span new="" roman="" style="font-family:" times=""> (MCL-1, BCL-XL) </span></span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">با اختلاف معناداری نسبت به گروه کنترل شد (</span></span><span dir="LTR" style="font-size:9.0pt"><span new="" roman="" style="font-family:" times="">(p <0.001</span></span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">.</span></span><span dir="LTR" style="font-size:9.0pt"><span style="font-family:"Times New Roman",serif"></span></span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:Calibri,sans-serif"><b><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">نتیجه</span></span></b><b><span dir="LTR" style="font-size:9.0pt">‌</span></b><b><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">گیری</span></span></b><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">:</span></span> <span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">به نظر می</span></span><span dir="LTR" style="font-size:9.0pt">‌</span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">رسد که استیگماسترول با تحقیق‌های بیشتر درباره خواص ضدسرطانی آن می</span></span><span dir="LTR" style="font-size:9.0pt">‌</span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">تواند به عنوان یک مکمل دارویی در درمان سرطان در کنار سایر روش</span></span><span dir="LTR" style="font-size:9.0pt">‌</span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">های درمانی رایج بهره ببرد.</span></span></span></span></span></span></span><br> &nbsp; <span style="font-size:11pt"><span style="line-height:115%"><span style="font-family:Calibri,sans-serif"><b><span style="font-size:10.0pt"><span style="line-height:115%"><span new="" roman="" style="font-family:" times="">Background and Aim:</span></span></span></b> <span style="font-size:10.0pt"><span style="background:white"><span style="line-height:115%"><span new="" roman="" style="font-family:" times="">Breast cancer is the most common type of cancer in women. One of the causes of cancer mortality is the increased anti-apoptotic activity of cancer cells. Phytosterols are a group of natural compounds that inhibit the growth of various cancer cells through various mechanisms. Stigmasterol, as one of the compounds in the phytosterols group, has anti-cancer effects. In the present study, the anti-tumor and apoptotic effects of stigmasterol on the expression of MCL-1 and BCL-XL genes in animal models of breast cancer were investigated.</span></span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:115%"><span style="font-family:Calibri,sans-serif"><b><span style="font-size:10.0pt"><span style="background:white"><span style="line-height:115%"><span new="" roman="" style="font-family:" times="">Methods:</span></span></span></span></b><span style="font-size:10.0pt"><span style="background:white"><span style="line-height:115%"><span new="" roman="" style="font-family:" times=""> In our experimental study, 15 BALB/C mice in 3 groups were transplanted subcutaneously with a breast tumor. The first group received 6 mg/kg stigmasterol, the second group received 20&nbsp;mg/kg cyclophosphamide, and the third group (control) received ethanol solution diluted with PBS (1:2) with intraperitoneal injection (IP). Tumor volume was measured for 10 days using digital caliper. Mice were then sacrificed and their tumor tissue was examined for changes in tumor size and the expression of BCL-XL and MCL-1 genes using real-time PCR.</span></span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:115%"><span style="font-family:Calibri,sans-serif"><b><span style="font-size:10.0pt"><span style="background:white"><span style="line-height:115%"><span new="" roman="" style="font-family:" times="">Results:</span></span></span></span></b><span style="font-size:10.0pt"><span style="background:white"><span style="line-height:115%"><span new="" roman="" style="font-family:" times=""> Treatment of tumor mice with stigmasterol reduced tumor size (*p<0.05) and also reduced the expression of anti-apoptotic genes (MCL-1, BCL-XL) with a significant difference as compared to the control group (***p <0.001).</span></span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:115%"><span style="font-family:Calibri,sans-serif"><b><span style="font-size:10.0pt"><span style="line-height:115%"><span new="" roman="" style="font-family:" times="">Conclusion:</span></span></span></b><span style="font-size:10.0pt"><span style="line-height:115%"><span new="" roman="" style="font-family:" times=""> Our findings indicate the anti-tumor and apoptotic properties of stigmasterol and introduces new insights into the production of effective natural compounds in the treatment of cancer.</span></span></span></span></span></span><br> &nbsp; استیگماسترول؛ سرطان پستان؛ ژنهای ‌ضدآپوپتوزی (MCL-1, BCL-XL). Stigmasterol, Breast Cancer, Anti-Apoptotic Genes (MCL-1, BCL-XL). 11 18 http://pejouhesh.sbmu.ac.ir/browse.php?a_code=A-10-1563-1&slc_lang=fa&sid=1 Mandana Ameli-Mojarad ماندانا عاملی مجرد 100319475328460026824 100319475328460026824 No Department of Biology- Faculty of Basic Sciences –Kharazmi University of Tehran, Iran. گروه بیولوژی، دانشکده علوم پایه، دانشگاه خوارزمی، تهران، ایران. Shima Jahani شیما جهانی 100319475328460026825 100319475328460026825 No Department of Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. گروه بیوشیمی، دانشکده پزشکی، دانشگاه علوم پزشکی شهید بهشتی، تهران، ایران Hussein Jahan-Tighi حسین جهان تیغی 100319475328460026826 100319475328460026826 No Department of Medicinal Plants, Agriculture- Jahad Organization of Sistan and Balouchestan Province, Zahedan, Iran. گروه گیاهان پزشکی، سازمان جهادکشاورزی سیستان و بلوچستان، زاهدان، ایران. Shokoofe Noori شکوفه نوری shnoori@sbmu.ac.ir 100319475328460026827 100319475328460026827 Yes Department of Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran گروه بیوشیمی بالینی، دانشکده پزشکی، دانشگاه علوم پزشکی شهید بهشتی، تهران، ایران.