کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2138694 1087883 2009 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Lentivirus-mediated RNA interference reversing the drug-resistance in MDR1 single-factor resistant cell line K562/MDR1
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Lentivirus-mediated RNA interference reversing the drug-resistance in MDR1 single-factor resistant cell line K562/MDR1
چکیده انگلیسی
Multidrug-resistance (MDR) is a major hindrance to successful chemotherapy. The emergence of MDR is multi-factorial. Among them, the MDR1 gene/P-glycoprotein (P-gp) is a popular and important reason. In our study, an MDR1 single-factorial drug-resistant leukemia cell line K562/MDR1 was constructed via transferring full-length human MDR1 cDNA into drug-sensitive K562 cells. The short-hairpin RNA (shRNA) targeting MDR1 gene was transfected into K562/MDR1 cell lines by the replication-defective lentiviral vector derived from HIV-1. The efficiency of RNA interference (RNAi) to silence the MDR1 gene and reverse multidrug-resistance in the MDR1 single-factor drug-resistance cell line K562/MDR1 was evaluated. The multi-factor resistant cell line K562/A02, induced by doxorubicin exposure, was used as a control. After RNA interference, the expression of the MDR1 gene and P-gp in K562/MDR1 was markedly down-regulated and the drug sensitivity was restored as IC50 values became similar to the K562 sensitive cell line. The expression of the MDR1 gene and P-gp in K562/A02 was markedly down-regulated too, and drug-resistance to anticancer drug is reduced to some extent but the IC50 was significantly higher than that of the sensitive cell line. These results demonstrated that lentivirus-mediated RNAi could efficiently down-regulate the expression of MDR1 and Pgp, and successfully reverse a cell's resistance to chemotherapeutic. Due to only MDR1 resistance, the K562/MDR1 cell showed much high specificity and thus is a better cell model for MDR1/P-gp research.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Leukemia Research - Volume 33, Issue 8, August 2009, Pages 1114-1119
نویسندگان
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