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Vol. 64 No. 15: Issue 15

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Ailanthone reverses multidrug resistance by inhibiting the P-glycoprotein-mediated efflux in resistant K562/A02 cells

https://doi.org/10.14715/cmb/2017.64.15.9
Fang Han
Hematology Department, Shengli Oilfield Central Hospital, No. 31 Ji'nan Road, Dongying District, Dongying, Shandong, 257034, China
Guoqiang Liu
Hematology Department, Shengli Oilfield Central Hospital, No. 31 Ji'nan Road, Dongying District, Dongying, Shandong, 257034, China
Caifeng Sun
Hematology Department, Shengli Oilfield Central Hospital, No. 31 Ji'nan Road, Dongying District, Dongying, Shandong, 257034, China
Jienan Wei
Department of Paediatrics, Shengli Oilfield Central Hospital, No. 31 Ji'nan Road, Dongying District, Dongying, Shandong, 257034, China

Corresponding Author(s) : Jienan Wei

pj1304@163.com

Cellular and Molecular Biology, Vol. 64 No. 15: Issue 15

Abstract

Multidrug resistance (MDR) poses a great impediment to cancer treatment. Excessive expression of ATP-binding cassette transport protein AC-1 (P-glycoprotein, P-GLP) is usually involved in MDR. In this study, ailanthone (AIL), a natural compound extracted from the whole seedlings of Ailanthus altissima (Simaroubaceae) was shown to mediate the reversal of P-GLP-induced MDR and restore the susceptibility of K562/A02 cells to doxorubicin (DOX). Further mechanistic studies revealed that AIL increased intracellular DOX accumulation and interrupted Rh123 efflux through suppression of P-GLP, and also suppressed P-GLP ATPase activity. At the same time, it markedly inhibited MDR1 gene expression and P-GLP protein to sensitize the cytotoxic effect of DOX. Furthermore, AIL down-regulated P-GLP expression by inhibiting the PI3K/Akt pathway. Thus, AIL could be a potential therapeutic compound for reversing P-GLP-mediated drug resistant cancer.

Keywords

Ailanthone multidrug resistance P-glycoprotein-mediated efflux in resistant K562/A02 cells.
Han, F., Liu, G., Sun, C., & Wei, J. (2018). Ailanthone reverses multidrug resistance by inhibiting the P-glycoprotein-mediated efflux in resistant K562/A02 cells. Cellular and Molecular Biology, 64(15), 55–61. https://doi.org/10.14715/cmb/2017.64.15.9
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