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Modulation of P-glycoprotein expression by triptolide in adriamycin-resistant K562/A02 cells.


Oncol Lett. 2012 Feb;3(2):485-489


Authors: Li H, Hui L, Xu W, Shen H, Chen Q, Long L, Zhu X


Abstract

Multidrug resistance is a serious obstacle encountered in leukemia treatment. Previous studies have found drug resistance in human leukemia is mainly associated with overexpression of the multidrug resistance gene 1 (MDR1). The aim of the present study was to investigate the modulation of P-glycoprotein expression by triptolide in adriamycin-resistant K562/A02 cells. The reverse effects of triptolide on drug resistance in K562/A02 cells were assessed by 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyl-tetrazolium bromide (MTT) assay. The percentage of apoptotic cells was obtained from annexin V/fluorescein isothiocyanate (FITC) and propridium iodide (PI) double-staining. The effects of triptolide on P-glycoprotein activity were evaluated by measuring intracellular adriamycin accumulation. The expression of P-glycoprotein was determined by flow cytometry. A luciferase reporter gene assay was used to detect the transcriptional activity of the MDR1 promoter. Results revealed that triptolide decreased the degree of resistance of K562/A02 cells, and significantly inhibited P-glycoprotein expression and drug-transport function, and increased the accumulation of adriamycin in K562/A02 cells as measured by flow cytometry. A luciferase reporter gene assay demonstrated that triptolide was capable of inhibiting the transcriptional activity of the MDR1 promoter. Triptolide may effectively reverse the adriamycin resistance in K562/A02 cells via modulation of the P-glycoprotein expression and by increasing intracellular adriamycin accumulation.

PMID: 22740937 [PubMed - as supplied by publisher]