Downregulation of NPM reverses multidrug resistance in human hepatoma cells via inhibition of P-glycoprotein expression

Luo,Fei; Li,Huiyu; Liang,Jianfang; Jia,Hongyan; Li,Xiaoyu; Xiao,Hong; He,Xuehua; He,Jiefeng; Tian,Yanzhang; Zhao,Haoliang

doi:10.3892/mmr.2017.6246

Downregulation of NPM reverses multidrug resistance in human hepatoma cells via inhibition of P-glycoprotein expression

Authors:
- Fei Luo
- Huiyu Li
- Jianfang Liang
- Hongyan Jia
- Xiaoyu Li
- Hong Xiao
- Xuehua He
- Jiefeng He
- Yanzhang Tian
- Haoliang Zhao
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Affiliations: Department of Breast Surgery, Shanxi Cancer Hospital, Taiyuan, Shanxi 030013, P.R. China, Department of General Surgery, Shanxi Academy of Medical Sciences, Shanxi Dayi Hospital, Taiyuan, Shanxi 030032, P.R. China, Department of Pathology, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China, Department of General Surgery, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China, Department of Molecular Biology, Shanxi Cancer Hospital, Taiyuan, Shanxi 030013, P.R. China, Department of Blood Transfusion, Shanxi Academy of Medical Sciences Shanxi Dayi Hospital, Taiyuan, Shanxi 030032, P.R. China
Published online on: February 24, 2017 https://doi.org/10.3892/mmr.2017.6246
Pages: 2360-2368

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Abstract

Multidrug resistance (MDR) is an important issue in current cancer treatments. In human cancer, drug resistance is primarily associated with the overexpression of multidrug resistance gene 1 (MDR1). Therefore, the human MDR1 gene promoter may be a target for anti‑MDR drug screening. Numerous methods to prevent MDR have been investigated. However, they have been proven to be clinically ineffective. Therefore, the aim of the present study was to investigate whether downregulation of nucleophosmin (NPM) demonstrates any effects on the reversal of MDR in hepatocellular carcinoma (HCC) cells. In the present study, two in vitro MDR HCC cell lines, HepG2/Adriamycin (ADM) and SMMC7721/ADM, were established and the level of MDR was measured. The results demonstrated that NPM downregulation markedly reversed the effects of MDR in the model used. In addition, NPM downregulation reduced P-glycoprotein expression, as well as MDR1 expression. These results suggested that downregulation of NPM may be a novel and effective method of reversing the effects of MDR, and may be a potential adjuvant for tumor chemotherapy.

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