Perfluorooctanoic acid stimulates breast cancer cells invasion and up-regulates matrix metalloproteinase-2/-9 expression mediated by activating NF-κB
Perfluorooctanoic acid stimulates breast cancer cells invasion and up-regulates matrix metalloproteinase-2/-9 expression mediated by activating NF-κB
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DOI：
10.1016/j.toxlet.2014.06.004
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发表时间：
2014-08-17
影响因子：
3.5
通讯作者：
Fu, Ziyi
中科院分区：
文献类型：
--
作者：
Zhang, Weidong;Wang, Fengliang;Fu, Ziyi
全氟辛酸（PFOA）因其耐污和防水的特性而被广泛使用。本研究旨在探讨PFOA刺激癌细胞侵袭及基质金属蛋白酶（MMPs）表达的分子机制。跨孔过滤实验表明，PFOA暴露（>= 5 nM）明显增强乳腺癌细胞MDA-MB-231的侵袭能力。荧光素酶报告基因分析、实时荧光定量PCR、western blotting和明胶酶谱分析均显示PFOA处理后细胞中MMP-2/-9 mRNA和蛋白水平均升高（P < 0.05）。Western blotting结果显示，PFOA可通过加速NF-kappa B向细胞核内转运而激活核因子κ B （NF-kappa B）。此外，在培养基中添加NF-kappa B抑制剂可以抑制乳腺癌细胞的侵袭性增强和MMP-2/-9的过表达。本研究提示PFOA可刺激乳腺癌细胞侵袭，通过激活NF-kappa B上调基质金属蛋白酶-2/-9的表达，值得更多的环境健康关注。2014爱思唯尔爱尔兰有限公司版权所有。
Perfluorooctanoic acid (PFOA) is widely used because of its stain-resistant and water-repellant properties. This study aimed to explore the molecular mechanisms undergoing the stimulation effects of PFOA on cancer cell invasion and matrix metalloproteinases (MMPs) expression. Trans-well filter assay showed that PFOA exposure (>= 5 nM) evidently enhanced the invasion ability of the breast cancer cells MDA-MB-231. Luciferase reporter assay, quantitative real-time PCR, western blotting and gelatin zymography consistently demonstrated that mRNA and protein levels of MMP-2/-9 were increased in the cells after PFOA treatment (P < 0.05 each). Western blotting revealed that PFOA could activate nuclear factor kappaB (NF-kappa B) by accelerating NF-kappa B translocation into the nucleus. Furthermore, addition of NF-kappa B inhibitor in culture medium could suppress the breast cancer cells invasiveness enhancement and MMP-2/-9 overexpression. This study indicates that PFOA can stimulate breast cancer cells invasion and up-regulate matrix metalloproteinase-2/-9 expression mediated by activating NF-kappa B, which deserves more environmental health concerns. (C) 2014 Elsevier Ireland Ltd. All rights reserved.