Perfluorooctanoic acid stimulates breast cancer cells invasion and up-regulates matrix metalloproteinase-2/-9 expression mediated by activating NF-κB.

Abstract

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-κB) by accelerating NF-κB translocation into the nucleus. Furthermore, addition of NF-κB 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-κB, which deserves more environmental health concerns.

• Authors: Weidong Zhang, Fengliang Wang, Pengfei Xu, Chen Miao, Xin Zeng, Xianwei Cui, Cheng Lu, Hui Xie, Hong Yin, Fei Chen, Jingjing Ma, Sheng Gao, Ziyi Fu
• Journal: Toxicology letters (Toxicol Lett) Vol. 229 Issue 1 Pg. 118-25 (Aug 17 2014) ISSN: 1879-3169 [Electronic] Netherlands
• PMID: 24960061 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Caprylates
• Coloring Agents
• Fluorocarbons
• Indicators and Reagents
• NF-kappa B
• RNA, Neoplasm
• Tetrazolium Salts
• Thiazoles
• perfluorooctanoic acid
• Luciferases
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9
• thiazolyl blue

Topics

• Blotting, Western
• Breast Neoplasms (pathology)
• Caprylates (pharmacology)
• Cell Line, Tumor
• Coloring Agents
• Female
• Fluorocarbons (pharmacology)
• Humans
• Indicators and Reagents
• Luciferases (metabolism)
• Matrix Metalloproteinase 2 (biosynthesis)
• Matrix Metalloproteinase 9 (biosynthesis)
• NF-kappa B (drug effects, metabolism)
• Neoplasm Invasiveness (pathology)
• RNA, Neoplasm (biosynthesis, genetics, isolation & purification)
• Real-Time Polymerase Chain Reaction
• Tetrazolium Salts
• Thiazoles
• Transcriptional Activation
• Up-Regulation