Long-term di (2-ethylhexyl)-phthalate exposure promotes proliferation and survival of HepG2 cells via activation of NFκB.
Long-term di (2-ethylhexyl)-phthalate exposure promotes proliferation and survival of HepG2 cells via activation of NFκB.
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长期暴露于邻苯二甲酸二(2-乙基己基)酯可通过激活 NF kappa B 促进 HepG2 细胞的增殖和存活
DOI：
10.1016/j.tiv.2017.04.015
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发表时间：
2017-08
影响因子：
3.2
通讯作者：
Ying Feng
中科院分区：
文献类型：
--
作者：
Ning Wei;Xiaoyan Feng;Zhiqin Xie;Yanan Zhan;Ying Feng
邻苯二甲酸二（2-乙基己基）酯（DEHP）是最常用的增塑剂。DEHP很容易从产品中浸出到环境中，已成为一种严重的环境污染物。然而，其对人类的致癌作用仍存在争议。在这项研究中，我们将肝细胞癌HepG 2细胞暴露于不同浓度的DEHP一段时间，然后结合RNA-seq分析和DEHP改变基因的分子分析。我们观察到，长期和极低剂量的DEHP处理在HepG 2细胞中具有生长诱导活性，而短期和高剂量的DEHP处理对肿瘤细胞增殖几乎没有影响。生物信息学分析进一步揭示，受DEHP影响的差异表达基因的大子集具有与炎症反应相关的功能注释。重要的是，我们发现长期DEHP处理刺激HepG 2细胞中的核因子-κ B（NF-κB）活性，而抑制NFκB活性可以抵消DEHP暴露的影响。结论：DEHP持续作用可通过激活NFκB信号通路促进HepG 2细胞增殖。
Di (2-ethylhexyl)-phthalate (DEHP) is the most commonly used plasticizer. DEHP can easily leach out from products into the environment and has become a significant environmental contamination. However, its carcinogenic effects in human remain controversial. In this study, we exposed hepatocellular carcinoma HepG2 cells to different concentrations of DEHP for a period of times, followed by a combination of RNA-seq analysis and molecular analysis for DEHP-altered genes. We observed that long-term and very low-dose DEHP treatment has growth-inducing activity in HepG2 cells, while short-term and high-dose DEHP treatment has little effects on tumor cell proliferation. Bioinformatic analysis further revealed that a large subset of differentially expressed genes affected by DEHP have functional annotations related to inflammation response. Importantly we found that long-term DEHP treatment stimulated nuclear factor-kappa B (NF-κB) activity in HepG2 cells, while inhibition of NFκB activity could offset the effects of DEHP exposure. In conclusion, continuous DEHP treatment could promote proliferation of HepG2 cells via activating NFκB signaling pathway.
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影响因子：
4.6
作者：
Mancini A;Di Segni C;Raimondo S;Olivieri G;Silvestrini A;Meucci E;Currò D
通讯作者：
Currò D
影响因子：
14.9
作者：
Wang K;Singh D;Zeng Z;Coleman SJ;Huang Y;Savich GL;He X;Mieczkowski P;Grimm SA;Perou CM;MacLeod JN;Chiang DY;Prins JF;Liu J
通讯作者：
Liu J
影响因子：
4.9
作者：
Fong, Jer-Pei;Lee, Fang-Jin;Lee, Ching-Chang
通讯作者：
Lee, Ching-Chang
DOI：
10.1038/nri3921
发表时间：
2015-12
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1016/0278-6915(89)90174-9
发表时间：
1989
期刊：
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
影响因子：
--
作者：
P. Schmezer
通讯作者：
P. Schmezer