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siRNA silences mdr1 gene expression and reverses apoptosis resistance of K562/ADM cells line

Wei Hu-lai GAO Li-ping JING Tao ZHAO Huai-shun Yi Juan Sun Jin HAN Jian Laboratory Center for Medical Science,Key Laboratory of Preclinical Study for New Drugs of Gansu Province,Lanzhou University,Lanzhou 730000,China  
Objective To explore the effect of small interfering RNA(siRNA)on silence of mdr1 gene and reversal of apoptosis resistance in muhidrug-resistant(MDR)human leukemia K562/ADM cell. Methods Human MDR leukemia cell line K562/ADM was used as the target cells.Two siRNAs(mdr1 siRNA-1 and mdrl siRNA-2)targeted mdrl gene were chemically synthesized and transfected into K562/ ADM cells with liposome.Expression of mdr1 mRNA was determined by real-time PCR,P-glycoprotein (P-gp)expression and caspase-3 activity were measured with flow cytometry(FCM),and the cell apoptosis was obserued by optical and electronic microscopy for morphology and Annexin V/PI staining.Results The mdr1 siRNA-1 and mdrl siRNA-2 could markedly down-regulate the expression of mdr1 gene in K562/ADM cells,the expression of mdr1 mRNA decreased by 91.2% and 82.0% ,and the P-gp by 74.1% and 84.4%,respectively.The caspase-3 activity was markedly enhanced,and the active caspase-3 in K562/ ADM cells increased by about 40% compared to liposome alone and non-silencing controls,the sensitivity of K562/ADM cells to adriamycin-induced apoptosis was significantly augmented,the apoptotic rate of the cells treated with siRNA plus adriamycin increased by about 60% compared to adriamycin alone.Conclusion siRNAs silence the expression of mdr1/P-gp to overcome the P-gp-mediated apoptosis resistance in drug-resistant K562/ADM cells.
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