Lentivirus-mediated RNA interference reversing the drug-resistance in MDR1 single-factor resistant cell line K562/MDR1
| Autor: | Wen-Tong Meng, Bohui Zheng, Yuping Gong, Xueshi Ye, Yamei Leng, Ting Liu |
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| Rok vydání: | 2009 |
| Předmět: |
Cancer Research
ATP Binding Cassette Transporter Subfamily B Genetic Vectors Cell Down-Regulation Models Biological physiological processes Viral vector Small hairpin RNA Mice RNA interference polycyclic compounds medicine Animals Humans ATP Binding Cassette Transporter Subfamily B Member 1 neoplasms P-glycoprotein Antibiotics Antineoplastic Leukemia biology RNA Hematology Transfection Molecular biology Drug Resistance Multiple medicine.anatomical_structure Oncology Doxorubicin Drug Resistance Neoplasm Cell culture HIV-1 NIH 3T3 Cells biology.protein RNA Interference K562 Cells |
| Zdroj: | Leukemia Research. 33:1114-1119 |
| ISSN: | 0145-2126 |
| Popis: | 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 IC(50) 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 IC(50) 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. |
| Databáze: | OpenAIRE |
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