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NF-E2相关因子2在抵抗煤焦油沥青诱导的BEAS-2B细胞恶性转化中起关键作用。

NF-E2-related factor 2 serves a key function in resistance to malignant transformation of BEAS-2B cells induced by coal tar pitch.

作者信息

Yu Songcheng, Yan Zhen, Feng Feifei, Ni Jing, Wang Wei, Nabie Kadijatu, Zhang Yiguo, Qu Lingbo, Wu Yongjun

机构信息

College of Public Health, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.

College of Medical Bioengineering and Faculty of Life Sciences, University of Chongqing, Chongqing 400044, P.R. China.

出版信息

Oncol Lett. 2018 Apr;15(4):5143-5148. doi: 10.3892/ol.2018.7924. Epub 2018 Feb 1.

Abstract

Coal tar pitch (CTP) is a key factor in the development of occupational lung cancer. In order to investigate the function of the anti-oxidative signaling pathway regulated by NF-E2-related factor 2 (Nrf2) during cancer development, BEAS-2B cells were cultured with CTP extract for 30 passages. It was revealed that malignant transformation occurred in cells between the 20 and 30th passage. The expression levels of Nrf2 and NAD(P)H:quinone oxidoreductase 1 (NQO1) were promoted throughout the CTP exposure culture, and there was a positive linear correlation between the expression levels of Nrf2 and NQO1. Following knockdown of Nrf2 expression, the level of NQO1 decreased markedly and malignant transformation was more likely to occur. It was hypothesized that CTP may be toxic to BEAS-2B cells, which may lead to malignant transformation. Nrf2 was a quick response factor: Counteracting cytotoxicity by promoting the expression of anti-oxidative genes. Thus, Nrf2 was associated with the malignant transformation of BEAS-2B cells exposed to CTP and may be a potential therapeutic target.

摘要

煤焦油沥青(CTP)是职业性肺癌发生发展的关键因素。为了研究核因子E2相关因子2(Nrf2)调控的抗氧化信号通路在癌症发生过程中的作用,将BEAS-2B细胞用CTP提取物培养30代。结果显示,在第20代至第30代细胞之间发生了恶性转化。在整个CTP暴露培养过程中,Nrf2和NAD(P)H:醌氧化还原酶1(NQO1)的表达水平均升高,且Nrf2和NQO1的表达水平之间存在正线性相关。敲低Nrf2表达后,NQO1水平显著降低,且更易发生恶性转化。推测CTP可能对BEAS-2B细胞有毒性作用,进而可能导致恶性转化。Nrf2是一个快速反应因子:通过促进抗氧化基因的表达来对抗细胞毒性。因此,Nrf2与暴露于CTP的BEAS-2B细胞的恶性转化有关,可能是一个潜在的治疗靶点。

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