Investigation of the mechanism involved in the As2O3-regulated decrease in MDR1 expression in leukemia cells.
Investigation of the mechanism involved in the As2O3-regulated decrease in MDR1 expression in leukemia cells.
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DOI：
10.3892/or.2013.2930
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发表时间：
2014-02
期刊：
影响因子：
4.2
通讯作者：
F. Gao;Jia Liu;W. Dong;W. Wang;Ying Wang;D. Cai;Zhihong Zheng;K. Sun
中科院分区：
文献类型：
--
作者：
F. Gao;Jia Liu;W. Dong;W. Wang;Ying Wang;D. Cai;Zhihong Zheng;K. Sun
Arsenic trioxide (As2O3) inhibits the expression of P-glycoprotein (P-gp) in leukemia cells; however, the mechanism behind this inhibition is unclear. The present study aimed to explore the effect of As2O3 on the expression and regulation of P-gp in leukemia cells, and elucidate the mechanism of the reversal of drug resistance. In the present study, electrophoretic mobility shift assay results indicated that p65 binds to the NF-κB binding site of MDR1, specifically in K562/D cells. Expression of p65 and phosphorylated IκB was reduced, while the expression of IκB was increased in K562/D cells treated with As2O3. The activity of luciferase increased up to 9-fold with 40 ng/ml TNF-α, and it was suppressed by ~25% following treatment with 1 µM As2O3. These findings suggest that As2O3 reverses the P-gp-induced drug resistance of leukemia cells through the NF-κB pathway. As2O3 may inhibit the activity of phosphorylase to inhibit IκB phosphorylation, thereby inhibiting NF-κB activity and MDR1 gene expression, leading to reversal of drug resistance.
