Nrf2/HO-1/HMGB1信号通路在白血病细胞K562/A02化疗耐药中的机制研究  

The Nrf2/HO-1/HMGB1 Signaling Pathway is Associated with Chemotherapy Resistance in K562/A02 Leukemia Cells

作　　者：赵明一[1] 李嘉欣[2,3] 陈志衡[1] 高飞[4] 赵平[4] 戴云鹏[4] 管国涛[4] 刘丽英[4] 

机构地区：[1]中南大学湘雅三医院儿科,湖南长沙410006 [2]南方医科大学第二临床学院,广东广州510515 [3]广东省心血管病研究所广东省人民医院广东省医学科学院,广东广州5100802 [4]山东大学附属省立医院儿科,山东济南250021

出　　处：《激光生物学报》2016年第2期129-135,共7页Acta Laser Biology Sinica

基　　金：国家自然科学基金(81200378;81500231);湖南省自然科学基金(13JJ6018;15JJ6118)

摘　　要：目的:通过观察高迁移率族蛋白1(HMGB1)、转录因子NF-E2相关因子2(Nrf2)及血红素加氧酶1(HO-1)基因沉默对白血病化疗耐药细胞(K562/A02细胞株)的影响,探讨该信号通路在白血病化疗耐药中的作用及其可能机制。方法:将HMGB1基因、Nrf2基因及HO-1基因的特异性干扰RNA分别转染阿霉素耐药细胞株K562/A02,荧光实时定量(RT-PCR)方法检测HMGB1、Nrf2及HO-1的mRNA表达水平,Western blot方法检测HMGB1、Nrf2及HO-1的蛋白表达水平,免疫荧光方法检测Nrf2的蛋白表达,并使用CCK-8方法检测转染前后K562/A02细胞株的细胞活性。结果:HMGB1基因、Nrf2基因或HO-1基因沉默的K562/A02细胞活性皆显著低于对照组及空白组(P<0.05),化疗敏感性恢复。结论:HMGB1高表达导致了白血病细胞株K562/A02对阿霉素的化疗耐药,Nrf2/HO-1信号通路参与了HMGB1诱导的K562/A02细胞的化疗耐药,其表达上调可恢复K562/A02细胞对阿霉素的敏感性。Objective: By silencing the high mobility group protein 1( HMGB1) gene,the nuclear factor erythroid 2-related factor 2( Nrf2) gene,and the heme oxygenase 1( HO-1) gene in chemotherapy-resistant leukemia cells( K562 /A02 cell line),to explore the role of the Nrf2 / HO-1 / HMGB1 signaling pathway in leukemia chemotherapy resistance and its possible mechanism. Methods: The Adriamycin-resistant cell line K562 / A02 were transfected with specific small interfering RNAs( siRNA) of HMGB1 gene,Nrf2 gene,and and HO-1 gene respectively. Fluorescence quantitative real-time polymerase chain reaction was used to examine the mRNA expression levels of HMGB1,Nrf2,and HO-1. Western blot was used to determine the protein expression levels of HMGB1,Nrf2,and HO-1. The Nrf2 protein expression level was detected by immunofluorescence assay. Cell viability of K562 / A02 cell line was analyzed by Cell Counting Kit-8 before and after transfection. Results: Silencing of HMGB1,Nrf2,or HO-1 in K562 / A02 cell line enhanced cell viability and recovered chemosensitivity compared with the control group and the blank group( P < 0. 05). Conclusions:HMGB1 overexpression in K562 / A02 cell line might lead to chemotherapy resistance to Adriamycin. The Nrf2 / HO-1signaling pathway might be involved in the HMGB1-induced chemotherapy resistance in K562 / A02 cell line,and its upregulation might recover chemosensitivity.

关 键 词：白血病 化疗耐药 多药耐药 高迁移率族蛋白1 转录因子NF-E2相关因子2 血红素加氧酶1 

分 类 号：R733.7[医药卫生—肿瘤]