Inhibition of the Nrf2-TrxR Axis Sensitizes the Drug-Resistant Chronic Myelogenous Leukemia Cell Line K562/G01 to Imatinib Treatments.
Nuclear factor erythroid 2-related factor 2 (Nrf2) is involved in tumor drug resistance, but its role in imatinib resistance of chronic myeloid leukemia (CML) remains elusive. We aimed to investigate the effects of Nrf2 on drug sensitivity, thioredoxin reductase (TrxR) expression, reactive oxygen sp...
| Publicado en: | BioMed Research International pp. 1 - 13 |
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| Autores principales: | , , , , , , , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
11/18/2019
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=139734909&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 139734909 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 23146133 FT2T jtl: BioMed Research International issn: 23146133 maglogo: N pubinfo: dt: 11/18/2019 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 139734909 139734909 139734909 10.1155/2019/6502793 139734909 ppf: 1 ppct: 12 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Inhibition of the Nrf2-TrxR Axis Sensitizes the Drug-Resistant Chronic Myelogenous Leukemia Cell Line K562/G01 to Imatinib Treatments. aug: au: Xu, Lianrong Zhao, Yan Pan, Fei Zhu, Mengxia Yao, Liqin Liu, Yan Feng, Jiangfang Xiong, Jie Chen, Xiuhua Ren, Fanggang Tan, Yanhong Wang, Hongwei affil: Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China sug: subj: Leukemia, Myeloid, Chronic Transcription Factors Gene Expression Drug Resistance, Neoplasm Imatinib Cell Line, Tumor Physiology Reactive Oxygen Species Oxidoreductases Apoptosis Cell Proliferation Proteins Physiology Genotype Pharmacogenetics Polymorphism, Genetic Antineoplastic Agents Pharmacodynamics MicroRNA Flow Cytometry Polymerase Chain Reaction Blotting, Western Signal Transduction ab: Nuclear factor erythroid 2-related factor 2 (Nrf2) is involved in tumor drug resistance, but its role in imatinib resistance of chronic myeloid leukemia (CML) remains elusive. We aimed to investigate the effects of Nrf2 on drug sensitivity, thioredoxin reductase (TrxR) expression, reactive oxygen species (ROS) production, and apoptosis induction in imatinib-resistant CML K562/G01 cells and explored their potential mechanisms. Stable K562/G01 cells with knockdown of Nrf2 were established by infection of siRNA-expressing lentivirus. The mRNA and protein expression levels of Nrf2 and TrxR were determined by real-time quantitative polymerase chain reaction and western blot, respectively. ROS generation and apoptosis were assayed by flow cytometry, while drug sensitivity was measured by the Cell Counting Kit-8 assay. Imatinib-resistant K562/G01 cells had higher levels of Nrf2 expression than the parental K562 cells at both mRNA and protein levels. Expression levels of Nrf2 and TrxR were positively correlated in K562/G01 cells. Knockdown of Nrf2 in K562/G01 cells enhanced the intracellular ROS level, suppressed cell proliferation, and increased apoptosis in response to imatinib treatments. Nrf2 expression contributes to the imatinib resistance of K562/G01 cells and is positively correlated with TrxR expression. Targeted inhibition of the Nrf2-TrxR axis represents a potential therapeutic approach for imatinib-resistant CML. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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