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Dioscin Restores the Activity of the Anticancer Agent Adriamycin in Multidrug-Resistant Human Leukemia K562/Adriamycin Cells by Down-Regulating MDR1 via a Mechanism Involving NF-魏B Signaling Inhibitio
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文摘
The purpose of this study was to investigate the ameliorating effect of dioscin (1) on multidrug resistance (MDR) in adriamycin (ADR)-resistant erythroleukemic cells (K562/adriamycin, K562/ADR) and to clarify the molecular mechanisms involved. High levels of multidrug resistance 1 (MDR1) mRNA and protein and reduced ADR retention were found in K562/ADR cells compared with parental cells (K562). Dioscin (1), a constituent of plants in the genus Discorea, significantly inhibited MDR1 mRNA and protein expression and MDR1 promoter and nuclear factor 魏-B (NF-魏B) activity in K562/ADR cells. MDR1 mRNA and protein suppression resulted in the subsequent recovery of intracellular drug accumulation. Additionally, inhibitor 魏B-伪 (I魏B-伪) degradation was inhibited by 1. Dioscin (1) reversed ADR-induced MDR by down-regulating MDR1 expression by a mechanism that involves the inhibition of the NF-魏B signaling pathway. These findings provide evidence to support the further investigation of the clinical application of dioscin (1) as a chemotherapy adjuvant.

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