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

Autor: Xuehua He, Fei Luo, Hong Xiao, Huiyu Li, Jiefeng He, Hao-Liang Zhao, Yan-Zhang Tian, Jianfang Liang, Hongyan Jia, Xiaoyu Li
Rok vydání: 2017
Předmět:
0301 basic medicine
Cancer Research
ATP Binding Cassette Transporter
Subfamily B

Carcinoma
Hepatocellular

Indoles
Down-Regulation
Antineoplastic Agents
Drug resistance
Pharmacology
Biochemistry
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
Cell Line
Tumor

Genetics
medicine
Humans
ATP Binding Cassette Transporter
Subfamily B
Member 1

RNA
Messenger

Molecular Biology
P-glycoprotein
integumentary system
Oncogene
biology
Cell Cycle
Liver Neoplasms
Nuclear Proteins
Cancer
Hep G2 Cells
Cell cycle
medicine.disease
Molecular medicine
Drug Resistance
Multiple

Gene Expression Regulation
Neoplastic

Multiple drug resistance
030104 developmental biology
Liver
Oncology
Doxorubicin
Drug Resistance
Neoplasm

030220 oncology & carcinogenesis
biology.protein
Molecular Medicine
Nucleophosmin
Zdroj: Molecular Medicine Reports. 15:2360-2368
ISSN: 1791-3004
1791-2997
DOI: 10.3892/mmr.2017.6246
Popis: 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.
Databáze: OpenAIRE