کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
9001696 1118546 2005 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Modulation of MDR1 gene expression in multidrug resistant MCF7 cells by low concentrations of small interfering RNAs
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی داروشناسی
پیش نمایش صفحه اول مقاله
Modulation of MDR1 gene expression in multidrug resistant MCF7 cells by low concentrations of small interfering RNAs
چکیده انگلیسی
MDR1 overexpression is one form of the multidrug resistance (MDR) phenotype, which can be acquired by patients initially responsive to chemotherapy. Because of the high toxicity of the inhibitors of P-glycoprotein (P-gp), the protein encoded by MDR1, attention has been focused on selective modulation of the MDR1 gene. Small interfering RNAs (siRNAs) were shown to be powerful tools for such a purpose, even when used at low concentrations (≤20 nM) in order to avoid sequence nonspecific effects. Two siRNAs used at 20 nM were shown to lead to efficient down-regulation of MDR1 at the protein level (only ca. 20% total P-gp expression remaining) in the doxorubicin selected MCF7-R human cell line. Cell surface expression of P-gp was inhibited, leading to reversal of the drug efflux phenotype (about 40% reversal with the most efficient siRNA) and enhancement of chemosensitivity (about 35%). At the mRNA level, the down-regulation of MDR1 obtained with the most efficient siRNA increased from about 50% (5 nM siRNA) to 60% (10 or 20 nM). The advantage of using a combination of siRNAs instead of a single one has been suggested.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 70, Issue 10, 15 November 2005, Pages 1424-1430
نویسندگان
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