Nrf2信号通路在亚砷酸钠诱导支气管上皮细胞恶性转化中的作用

发布时间：2018-01-11 15:17

本文关键词：Nrf2信号通路在亚砷酸钠诱导支气管上皮细胞恶性转化中的作用　出处：《卫生研究》2016年03期 　论文类型：期刊论文

【摘要】：目的构建亚砷酸钠(NaAsO_2)诱导人支气管上皮(HBE)细胞恶性转化的模型,探讨核转录因子-E2类相关因子2(Nrf2)信号通路在恶性转化过程中的作用。方法以2.5μmol/L NaAsO_2染毒HBE细胞,以四氮唑盐比色(MTT)法、克隆形成和划痕侵袭等实验鉴定细胞恶性转化;蛋白免疫印迹实验检测恶性转化过程中细胞内Nrf2及其下游靶基因醌氧化还原酶1(NQO1)和血红素单加氧酶-1(HO-1)的表达水平。结果随NaAsO_2染毒代数的增加,HBE细胞逐渐表现增殖失控,染毒25代(As-HBE-T25)和50代(As-HBE-T50)的克隆形成率分别为1.33%和4.47%,侵袭能力为正常HBE的2.04倍和4.17倍;同时,细胞浆和细胞核中的Nrf2表达水平均下降,As-HBE-T25细胞浆和细胞核中的Nrf2表达水平分别为正常HBE的0.83倍和0.81倍,As-HBE-T50为0.42倍和0.63倍;NQO1在As-HBE-T25和As-HBE-T50中的表达为正常HBE的0.84倍和0.59倍,HO-1则为0.75倍和0.48倍(P0.05)。结论 NaAsO_2慢性染毒诱导了人支气管上皮细胞恶性转化,可能的机制为NaAsO_2持续抑制Nrf2信号通路,使NQO1和HO-1表达水平降低,从而引起细胞恶性增殖。
[Abstract]:Objective to establish a model of malignant transformation of human bronchial epithelial (HBE) cells induced by sodium arsenite (NaAsO _ 2). To investigate the role of nuclear transcription factor-E2 related factor 2nrf2) signaling pathway in the process of malignant transformation. Methods HBE cells were exposed to 2.5 渭 mol/L NaAsO_2. The malignant transformation of the cells was identified by MTT assay, clone formation and scratch invasion. Detection of Nrf2 and its downstream target gene quinone redox enzyme 1 (NQO1) and heme monooxygenase-1 (HO-1) during malignant transformation by Western blot. Results increased with NaAsO_2 exposure algebra. The proliferation of HBE cells was out of control gradually, and the clone formation rates of As-HBE-T25 and As-HBE-T50 were 1.33% and 4.47%, respectively. The invasiveness of HBE was 2.04 and 4.17 times higher than that of normal HBE. At the same time, the expression of Nrf2 in cytoplasm and nucleus decreased. The expression of Nrf2 in cytoplasm and nucleus of As-HBE-T25 cells was 0.83 and 0.81 times higher than that of normal HBE, respectively. As-HBE-T50 was 0.42 and 0.63 times; The expression of NQO1 in As-HBE-T25 and As-HBE-T50 was 0.84 and 0.59 times higher than that in normal HBE. HO-1 was 0.75 times and 0.48 times (P 0.05). Conclusion chronic exposure to NaAsO_2 can induce malignant transformation of human bronchial epithelial cells. The possible mechanism is that NaAsO_2 continuously inhibits the Nrf2 signaling pathway and reduces the expression of NQO1 and HO-1, which leads to the malignant proliferation of cells.
【作者单位】：四川大学华西公共卫生学院环境卫生学教研室;
【基金】：国家自然科学基金面上项目(No.81372945)
【分类号】：R114
【正文快照】： 肺癌是人类最常见的恶性肿瘤,高居各种肿瘤死因的首位。大量研究显示,长期低水平砷暴露能够增高罹患肺癌的风险[1],但砷导致肺癌发生发展的确切机制尚未完全阐明。目前,在砷毒性机制研究中,氧化应激学说被普遍接受和广泛研究[2-3]。核转录因子-E2类相关因子2(nuclearfactor er

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