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首页> 外文期刊>Toxicology and Applied Pharmacology >Molecular mechanisms of 3,3 ' 4,4 ',5-pentachlorobiphenyl-induced epithelial-mesenchymal transition in human hepatocellular carcinoma cells
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Molecular mechanisms of 3,3 ' 4,4 ',5-pentachlorobiphenyl-induced epithelial-mesenchymal transition in human hepatocellular carcinoma cells

机译：3,3'4,4'，5-五氯丙烯基诱导的人肝细胞癌细胞上皮 - 间充质转变的分子机制

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摘要

Polychlorinated biphenyls (PCBs) are classic persistent organic pollutants (POPs). Many studies have found a positive association between the progression of hepatocellular carcinoma (HCC) and PCBs exposure. However, the influence of PCBs on epithelial-mesenchymal transition (EMT) of HCC remains to be unclear. In this study, we explored the effect of PCB126 on EMT in HCC cells and its underlying mechanisms. The data showed that PCB126, exposing both Bel-7402 and SMMC-7721 cells for 48 h, promoted EMT that was demonstrated by E-cadherin repression, up-regulation of N-cadherin and vimentin, and morphological alteration. We found that signal transducer and activator of transcription 3 (STAT3)/Snail1 signaling was activated after PCB126 exposure, and the addition of STAT3 inhibitor WP1066 blocked PCB126-induced down-regulation of E-cadherin as well as up regulation of N-cadherin and vimentin. Moreover, PCB126 exposure increased pyruvate kinase M2 (PKM2) expression and its nuclear translocation, whereas treatment with PKM2 shRNA suppressed the activation of STAT3/Snail1 signaling and the alternation of EMT-related molecules (E-cadherin, N-cadherin and vimentin). Furthermore, this study indicated estrogen receptor (ER) and aryl hydrocarbon receptor (AhR) were involved in PCB126-induced effects on PKM2, STAT3/Snail1 signaling and EMT by according treatment using ER inhibitor ICI and AhR shRNA. Notably, PCB126-increased reactive oxygen species (ROS) production via AhR is associated with activation of PKM2/STAT3/Snail1 cascades and contributes to EMT. Taken together, these results indicated that PCB126 promotes EMT process of HCC cells via PKM2/STAT3/Snail1 signaling which is mediated by ER and AhR. (C) 2017 Elsevier Inc. All rights reserved.
机译：多氯联苯（PCBs）是典型的持久性有机污染物（POPs）。许多研究发现，肝细胞癌（HCC）的进展与接触多氯联苯呈正相关。然而，多氯联苯对肝癌上皮-间充质转化（EMT）的影响尚不清楚。在本研究中，我们探讨了PCB126对肝癌细胞EMT的影响及其潜在机制。数据显示，PCB126同时暴露于Bel-7402和SMMC-7721细胞48小时后，可促进EMT，其表现为E-钙粘蛋白抑制、N-钙粘蛋白和波形蛋白上调以及形态学改变。我们发现，PCB126暴露后，信号转导子和转录激活子3（STAT3）/Snail1信号被激活，STAT3抑制剂WP1066的加入阻断了PCB126诱导的E-钙粘蛋白下调以及N-钙粘蛋白和波形蛋白上调。此外，PCB126暴露增加了丙酮酸激酶M2（PKM2）的表达及其核易位，而PKM2 shRNA治疗抑制了STAT3/Snail1信号的激活和EMT相关分子（E-钙粘蛋白、N-钙粘蛋白和波形蛋白）的交替。此外，本研究还表明，雌激素受体（ER）和芳香烃受体（AhR）参与了PCB126诱导的PKM2、STAT3/Snail1信号传导和EMT效应，通过使用ER抑制剂ICI和AhR shRNA进行相应治疗。值得注意的是，通过AhR增加的活性氧（ROS）生成与PKM2/STAT3/Snail1级联的激活有关，并有助于EMT。综上所述，这些结果表明PCB126通过PKM2/STAT3/Snail1信号途径促进肝癌细胞的EMT过程，该信号由ER和AhR介导。（C） 2017爱思唯尔公司版权所有。

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