fa افزایش زنده‌مانی در لوسمی لنفوبلاستیک حاد تحت درمان با متوترکسات به‌واسطه DR5 و کاسپاز-8 در شرایط هیپرگلیسمی سلولی و مولکولی Cellular and Molecular مقاله اصیل پژوهشی Original Article <div style="text-align: justify;"><span style="font-size:10pt"><span style="direction:rtl"><span style="unicode-bidi:embed"><span new="" roman="" style="font-family:" times=""><b><span b="" lang="AR-SA" mitra="" style="font-family:">زمینه و هدف:</span></b> <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">نظر به مقاومت دارویی شیمی درمانی در مبتلایان به دیابت و شیوع بیماری </span></span><span lang="AR-SA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">لوسمی لنفوبلاستیک حاد</span></span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> در آن‌ها، هدف مطالعه حاضر، بررسی اثر هیپرگلوکز بر بیان ژن های </span></span>DR5 <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">و </span></span>Caspase-8<span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> در سلول‌های لنفوبلاستیک (</span></span>NALM-6<span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">)&nbsp;</span></span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">و ارتباط آن به پاسخ سلول‌ها نسبت به متوترکسات است</span></span><span dir="LTR" style="font-size:9.0pt">.</span><span lang="AR-SA" style="font-size:11.0pt"><span style="font-family:"B Mitra""></span></span></span></span></span></span><br> <span style="font-size:10pt"><span style="direction:rtl"><span style="unicode-bidi:embed"><span new="" roman="" style="font-family:" times=""><b><span b="" lang="AR-SA" mitra="" style="font-family:">روش تحقیق: </span></b><span lang="AR-SA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">در این مطالعه تجربی</span></span> <span lang="AR-SA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">ابتدا</span></span> <span lang="AR-SA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">سلول&shy;های </span></span>NALM-6<span style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> در چهار گروه</span></span><span lang="AR-SA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> کنترل (</span></span>C<span lang="AR-SA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">)، سلول‌های تیمار شده با متوترکسات (</span></span>C+M<span lang="AR-SA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">)</span></span><span lang="AR-SA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">، سلول&shy; های تیمار شده در محیط با غلظت</span></span> <span lang="AR-SA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">گلوکز بالا (</span></span>G<span lang="AR-SA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">)، سلول‌های تیمارشده در محیط با غلظت گلوکز بالا و متوترکسات (</span></span>G+M<span lang="AR-SA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">)</span></span>&nbsp;<span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">در محیط </span></span>RPMI 1640<span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> و </span></span>FBS 10%<span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> حاوی آنتی‌بیوتیک کشت داده شد. میزان حیات سلول‌های تیمار شده با متوترکسات، به روش </span></span>MTT<span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> بررسی و سپس با روش </span></span>RT- qPCR<span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> بیان نسبی ژن&shy;‌های </span></span>DR5<span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> و&nbsp;</span></span>Caspase-8<span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> اندازه‌گیری گردید.</span></span><span lang="AR-SA" style="font-size:11.0pt"><span style="font-family:"B Mitra""></span></span></span></span></span></span><br> <span style="font-size:10pt"><span style="direction:rtl"><span style="unicode-bidi:embed"><span new="" roman="" style="font-family:" times=""><b><span b="" lang="AR-SA" mitra="" style="font-family:">یافته‌ها:</span></b> <span lang="AR-SA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">گروه </span></span><span dir="LTR" style="font-size:9.0pt">M</span><span lang="AR-SA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> درمقایسه با گروه </span></span><span dir="LTR" style="font-size:9.0pt">C</span><span lang="AR-SA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> 50% زنده‌مانی و گروه </span></span><span dir="LTR" style="font-size:9.0pt">G+M</span><span style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> در مقایسه با گروه کنترل </span></span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">58%</span></span><span lang="AR-SA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> زنده‌مانی داشتند.</span></span> <span lang="AR-SA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">بیان ژن</span></span>DR5 <span lang="AR-SA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">در گروه </span></span><span dir="LTR" style="font-size:9.0pt">G+M</span><span lang="AR-SA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> در مقایسه با گروه </span></span><span dir="LTR" style="font-size:9.0pt">G</span> <span lang="AR-SA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">تفاوت معنی‌داری نداشت (0/05<p)< span=""></p)<></span><span lang="AR-SA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">، </span></span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">اما </span></span><span lang="AR-SA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">بیان ژن کاسپاز-8 درگروه </span></span><span dir="LTR" style="font-size:9.0pt">G</span><span lang="AR-SA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> با گروه کنترل (0/01>P) و در گروه </span></span><span dir="LTR" style="font-size:9.0pt">G</span><span lang="AR-SA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> در مقایسه با گروه سلول‌های تیمار‌شده&nbsp;(0/001>P) </span></span><span lang="AR-SA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">به‌طور معنی‌داری پایین‌تر بود.</span></span></span></span></span></span><br> <span style="font-size:10pt"><span style="direction:rtl"><span style="unicode-bidi:embed"><span new="" roman="" style="font-family:" times=""><b><span b="" lang="AR-SA" mitra="" style="font-family:">نتیجه‌گیری:</span></b><span lang="AR-SA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> یافته‌ها نشان داد میزان زنده‌مانی سلول‌های (</span></span>NALM-6<span lang="AR-SA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">) در غلظت بالای گلوکز بعد از تیمار با متوترکسات، بیش از حالت مشابه در گروه کنترل بوده که بیانگر اثر مقاومت‌زایی گلوکز بر درمان با دارو است.</span></span></span></span></span></span></span></div> <div style="text-align: justify;"><span style="font-size:10pt"><span new="" roman="" style="font-family:" times=""><b><span style="font-size:11.0pt">Background and Aims:</span></b><span style="font-size:11.0pt"> Considering the drug resistance of chemotherapy in diabetic patients and the prevalence of acute lymphoblastic leukemia in them, the present study aimed to investigate the effect of hyperglucose condition on the expression of DR5 and Caspase-8 genes in lymphoblastic cells (NALM-6) and its relationship to the cells&#39; response to methotrexate.</span><span style="font-size:11.0pt"></span></span></span><br> <span style="font-size:10pt"><span new="" roman="" style="font-family:" times=""><b><span style="font-size:11.0pt">Materials and Methods:</span></b><span style="font-size:11.0pt"> In this in vitro study, NALM-6 cells were cultured in RPMI 1640 medium with 10% fetal bovine serum (FBS) containing antibiotics across four control groups: cells in the control group (C), cells treated with methotrexate (C+M), cells treated in an environment with high glucose concentration (G), and cells treated in an environment with high glucose concentration and methotrexate (G+M). The treated cells were subjected to hyperglucose conditions for 10 days in an environment with high glucose concentration. The survival rate of methotrexate-treated cells was evaluated by the MTT method, and then the relative expression of DR5 and Caspase-8 genes was measured by the RT-qPCR method. The statistical significance was defined as a P-value less than 0.05.</span></span></span><br> <span style="font-size:10pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span new="" roman="" style="font-family:" times=""><b><span style="font-size:11.0pt">Results:</span></b><span style="font-size:11.0pt"> The M group had 50% survival compared to the control group, and the G+M group had 58% survival compared to the control group. The expression of the DR5 gene in the group G+M compared to the G group was not significantly different (P>0.05); however, the expression of the caspase-8 gene in the G group was significantly lower compared to the control group (P<0.01) and also lower in the G group compared to the treated cells (P<0.001).</span></span></span></span></span><br> <span style="font-size:10pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span new="" roman="" style="font-family:" times=""><b><span style="font-size:11.0pt">Conclusion:</span></b><span style="font-size:11.0pt"> The findings indicated that the survival rate of NALM-6 cells in high concentrations of glucose after treatment with methotrexate was higher than the same condition in the control group, which indicates the effect of glucose resistance on drug treatment.</span></span></span></span></span></div> لوسمی لنفوبلاستیک حاد, Caspase-8, دیابت, DR5, متوترکسات Acute Lymphoblastic Leukemia, Caspase-8, Diabetes, DR5, Methotrexate 195 204 http://journal.bums.ac.ir/browse.php?a_code=A-10-3567-2&slc_lang=fa&sid=1 Kosar Kiafar کوثر کیافر Erfaneh.kiafar98@gmail.com 8700319475328460049441 0009-0002-6623-5286 No Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran مرکز تحقیقات سلولی و مولکولی، دانشگاه علوم پزشکی بیرجند، بیرجند، ایران Mahtab Sayadi مهتاب صیادی sayadi.mahtab@yahoo.com 8700319475328460049442 8700319475328460049442 No Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran مرکز تحقیقات سلولی و مولکولی، دانشگاه علوم پزشکی بیرجند، بیرجند، ایران Forouzan Karam فروزان کرم forouzankaram18@gmail.com 8700319475328460049443 8700319475328460049443 No Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran مرکز تحقیقات سلولی و مولکولی، دانشگاه علوم پزشکی بیرجند، بیرجند، ایران Behzad Mesbahzadeh بهزاد مصباح زاده mesbahmoeen@yahoo.com 8700319475328460049444 8700319475328460049444 Yes Cardiovascular Diseases Research Center, Department of Physiology, Birjand University of Medical Sciences, Birjand, Iran مرکز تحقیقات بیماری‌های قلب و عروق، گروه فیزیولوژی پزشکی، دانشکده پیراپزشکی، دانشگاه علوم پزشکی بیرجند، بیرجند، ایران