سرکوب MCL-1 بوسیله RNA کوچک مداخله گرباعث حساسیت به اتوپساید در U937 می شود

SILENCING OF MYELOID CELL LEUKEMIA-1 (MCL-1) BY SMALL INTERFERENCE RNA IMPROVES CHEMOSENSITIVITY TO ETOPOSIDE IN U-937 LEUKEMIC CELLS


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نویسندگان: بهزاد برادران

کلمات کلیدی: Mcl-1, siRNA, etoposide, U-937 cells

نشریه: 55283 , 30 , 1 , 2016

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نویسنده ثبت کننده مقاله بهزاد برادران
مرحله جاری مقاله تایید نهایی
دانشکده/مرکز مربوطه مرکز تحقیقات ایمونولوژی
کد مقاله 58715
عنوان فارسی مقاله سرکوب MCL-1 بوسیله RNA کوچک مداخله گرباعث حساسیت به اتوپساید در U937 می شود
عنوان لاتین مقاله SILENCING OF MYELOID CELL LEUKEMIA-1 (MCL-1) BY SMALL INTERFERENCE RNA IMPROVES CHEMOSENSITIVITY TO ETOPOSIDE IN U-937 LEUKEMIC CELLS
ناشر 7
آیا مقاله از طرح تحقیقاتی و یا منتورشیپ استخراج شده است؟ خیر
عنوان نشریه (خارج از لیست فوق)
نوع مقاله Original Article
نحوه ایندکس شدن مقاله ایندکس شده سطح یک – ISI - Web of Science
آدرس لینک مقاله/ همایش در شبکه اینترنت Silencing of myeloid cell leukemia-1 by small interfering RNA improves chemosensitivity to etoposide in u-937 leukemic cells.

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A key issue in the treatment of acute myeloid leukemia (AML) is the development of drug resistance to chemotherapeutic agents. Overexpression of myeloid cell leukemia-1 (Mcl-1), an anti-apoptotic protein, is associated with tumor progression and drug resistance in leukemia and several cancers. The purpose of this study was to investigate the effect of specific Mcl-1 small interference RNA (siRNA) on the proliferation and chemosensitivity of U-937 AML cell to etoposide. The siRNA transfection was conducted using Lipofectamine™ 2000. Quantitative real-time RT-PCR (qRT-PCR) and Western blot analysis were employed to measure the expression levels of mRNA and protein, respectively. To evaluate tumor cell growth after siRNA transfection, Trypan blue exclusion assay was conducted. The cytotoxic effects of siRNA and etoposide were determined using MTT assay on their own and in combination. DNA-histone ELISA and annexin-V/FITC assays were performed to study the apoptosis. Mcl-1 siRNA transfection significantly blocked the expression of Mcl-1 mRNA and protein in a time-dependent manner, leading to a strong growth inhibition and enhanced apoptosis (P less than 0.05). Furthermore, pretreatment with Mcl-1 siRNA, synergistically enhanced the cytotoxic and apoptotic effects of etoposide (P less than 0.05). Our results demonstrated that Mcl-1 plays a fundamental role in the survival and resistance of U-937 cells to etoposide. Therefore, Mcl-1 can be considered an attractive target in gene therapy of AML patients and siRNA-mediated silencing of this gene may be a novel strategy in AML treatment.

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141-SILENCING OF MYELOID CELL LEUKEMIA-1 (MCL-1) BY SMALL INTERFERENCE.pdf1395/06/221279351دانلود