fa اثر ضد سرطانی عصاره آرتمیزیا و داروی سیس پلاتین در القای آپوپتوز و مهار تکثیرسلول‌هایA2780 سرطان تخمدان انسان علوم سلولی و مولکولی Cell and Molecular Biology مقاله پژوهشی Original Article <span style="font-size:11pt"><span style="line-height:normal"><span style="text-autospace:none"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:Calibri,sans-serif"><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">سیس پلاتین به عنوان یک داروی شیمی درمانی بدلیل عوارض جانبی در مراحل پیشرفته بیماری مشکلاتی ایجاد می‌کند. اخیراً گیاه آرتمیزیا به‌دلیل داشتن ترکیبات فعال زیستی، اثرات ضد تکثیری و ضد التهابی مورد توجه قرار گرفته است. هدف از این تحقیق بررسی اثر ضد سرطانی و آنتی متاستازی گیاه آرتمیزیا و سیس پلاتین به تنهایی و به صورت ترکیبی در رده سلولی </span></span><span dir="LTR" lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">A2780</span></span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:"> سرطان تخمدان انسان است. زیستایی سلول‌های </span></span><span dir="LTR" lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">A2780</span></span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:"> پس از تیمار با عصاره متانولی اندام‌های هوایی آرتمیزیا، سیس پلاتین و تواًم آن توسط آزمون </span></span><span dir="LTR" lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">MTT</span></span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:"> ارزیابی شد و تغییرات ریخت‌شناسی هسته سلول با رنگ آمیزی </span></span><span dir="LTR" lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">DAPI</span></span> <span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">بررسی شد. القای آپوپتوز توسط آزمون انکسین، اثرات ضد تهاجمی به وسیله سنجش مهاجرت سلولی و تغییرات سطح بیان ژن‌های آپوپتوزی (</span></span><span dir="LTR" lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">Bax</span></span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:"> و </span></span><span dir="LTR" lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">P53</span></span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">) و ژن‌های درگیر در متاستاز&nbsp; (</span></span><span dir="LTR" lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">MMP2</span></span> <span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">و </span></span><span dir="LTR" lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">MMP9</span></span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">) با استفاده از </span></span><span dir="LTR" lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">Real-time PCR</span></span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:"> مورد سنجش قرار گرفت. داده‌های آزمایش </span></span><span dir="LTR" lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">MTT</span></span><b>&nbsp; </b><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">نشان<b> </b>داد که عصاره آرتمیزیا، سیس پلاتین و تواًم آن منجر به مرگ نیمی از سلول‌ها شدند. تست </span></span><span dir="LTR" lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">DAPI</span></span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:"> و انکسین </span></span><span dir="LTR" lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">V</span></span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">، قطعه قطعه شدن </span></span><span dir="LTR" lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">DNA</span></span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:"> و افزایش درصد آپوپتوز سلولی نسبت به گروه کنترل را نشان داد. در آزمون مهاجرت و</span></span><span dir="LTR" lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times=""> Real-time PCR </span></span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">&nbsp;غلظت‌های تیماری منجر به کاهش تهاجم، افزایش بیان ژن‌های آپوپتوزی (</span></span><span dir="LTR" lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">Bax</span></span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:"> و </span></span><span dir="LTR" lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">P53</span></span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">) و کاهش بیان ژن‌های درگیر در متاستاز (</span></span><span dir="LTR" lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">MMP2</span></span> <span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">و </span></span><span dir="LTR" lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">MMP9</span></span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">) در سلول‌های سرطانی شدند. نتایج این پژوهش نشان داد که عصاره</span></span> <span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">گیاه</span></span> <span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">آرتمیزیا</span></span> <span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">و</span></span> <span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">داروی</span></span> <span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">سیس پلاتین به تنهایی</span></span> <span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">دارای</span></span> <span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">اثر</span></span> <span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">ضد</span></span> <span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">تکثیری،</span></span> <span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">القا کننده</span></span> <span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">آپوپتوز</span></span> <span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">و دارای اثر آنتی</span></span> <span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">متاستازی</span></span> <span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">مناسب</span></span> <span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">در</span></span> <span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">رده</span></span> <span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">سلولی</span></span><span dir="LTR" lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times=""> A2780 </span></span><span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">است. همچنین، استفاده</span></span> <span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">توأم</span></span> <span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">از</span></span> <span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">این گیاه</span></span> <span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">همراه</span></span> <span lang="AR-SA" 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:">سیس پلاتین</span></span> <span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">علاوه بر داشتن اثرات مذکور باعث</span></span> <span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">کاهش</span></span> <span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">غلظت</span></span> <span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">سیس پلاتین</span></span> <span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">و عوارض</span></span> <span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">جانبی</span></span> <span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">ناشی</span></span> <span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">از</span></span> <span lang="AR-SA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">آن در درمان این بیماری می‌شود</span></span><span dir="LTR" lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">.</span></span><span lang="EN-CA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:"> <i>&nbsp;</i></span></span><b><span dir="LTR" lang="EN-CA" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"></span></span></b></span></span></span></span></span></span><br /> <span style="font-size:11pt"><span style="line-height:normal"><span style="text-autospace:none"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:Calibri,sans-serif"><b><span dir="LTR" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times=""><span style="color:black"></span></span></span></b></span></span></span></span></span></span><br /> &nbsp; <span lang="EN-CA" style="font-size:10.0pt"><span style="line-height:115%"><span new="" roman="" style="font-family:" times="">Cisplatin, as a chemotherapy drug, causes serious side effects in the advanced stages of the cancer. Recently, <i>Artemisia</i> has been considered for its bioactive compounds, anti-proliferative and anti-inflammatory effects. The aim of this study was to evaluate the anti-cancer and anti-metastatic effects of the methanolic extract of aerial organs of Artemisia and cisplatin, either alone or in combination, in human ovarian cancer cell line A2780.</span></span></span> <span lang="EN-CA" style="font-size:10.0pt"><span style="line-height:115%"><span new="" roman="" style="font-family:" times="">The viability of A2780 cells after treatment with Artemisia extract, cisplatin and their combination was evaluated by MTT assay and the alterations in the morphology of the cell nuclei were examined by DAPI staining. The induction of apoptosis was assessed by Annexin V test, cell migration and changes in expression levels of apoptotic genes (Bax and P53) and metastasis (MMP2 and MMP9) using real-time PCR.</span></span></span> <span lang="EN-CA" style="font-size:10.0pt"><span style="line-height:115%"><span new="" roman="" style="font-family:" times="">MTT test data showed that Artemisia extract, cisplatin and their combination decreased the viability of ovarian cancer cells. DAPI and Annexin V indicated the DNA fragmentation and&nbsp;</span></span></span><span style="font-size:11pt"><span style="line-height:normal"><span style="font-family:Calibri,sans-serif"><span lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">increased percentage of cellular apoptosis in comparison with the control group. The migration and real-time PCR data showed a decline in thr cell invasion and expression of genes involved in metastasis (MMP2 and MMP9)</span></span> <span lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">in cancer cells while the expression of apoptotic genes (Bax and P53) was increased in the treated groups.</span></span> <span lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">The results of this study showed that while both Artemisia extract and cisplatin posses anti-proliferative effect, apoptotic and suitable anti-metastatic effects on their own in A2780 cell line, their combination have synergic effects and posses those desired properties in lower concentration of cisplatin, which can reduce the side effects of cisplatin in cancer treatment. </span></span></span></span></span><br /> <span style="font-size:11pt"><span style="line-height:normal"><span style="font-family:Calibri,sans-serif"><b><span style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"></span></span></b></span></span></span><br /> &nbsp; آزمون انکسین ,آزمون مهاجرت, ترکیبات فعال زیستی ,ریخت شناسی هسته سلول ,زیستایی سلول  Annexin test, Bioactive compounds, Cell biology, Cell nucleus morphology, Immigration test 246 256 http://nbr.khu.ac.ir/browse.php?a_code=A-10-39-3&slc_lang=fa&sid=1 Neda Rezazadeh ندا رضازاده n.rezazadeh75@gmail.com 100319475328460010889 100319475328460010889 No Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran گروه زیست شناسی، واحد مشهد، دانشگاه آزاد اسلامی، مشهد، ایران Javad Baharara جواد بهارآرا baharara@mshdiau.ac.ir 100319475328460010890 100319475328460010890 Yes Department of Biology and Applied Biology Research Center of Animal Development, Mashhad Branch, Islamic Azad University, Mashhad, Iran گروه زیست شناسی و مرکز تحقیقات بیولوژی کاربردی تکوین جانوری، واحد مشهد، دانشگاه آزاد اسلامی، مشهد،ایران Khadijeh Nejad Shahrokhabadi خدیجه نژاد شاهرخ آبادی shahrokhabady@yahoo.com 100319475328460010891 100319475328460010891 No Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran گروه زیست شناسی، واحد مشهد، دانشگاه آزاد اسلامی، مشهد، ایران