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

Toxicol Lett. 2014 Aug 17;229(1):118-25. doi: 10.1016/j.toxlet.2014.06.004. Epub 2014 Jun 21.

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.

Keywords: Breast cancer; Invasion; Perfluorooctanoic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*
  • NF-kappa B / metabolism
  • Neoplasm Invasiveness / pathology*
  • RNA, Neoplasm / biosynthesis
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / isolation & purification
  • Real-Time Polymerase Chain Reaction
  • Tetrazolium Salts
  • Thiazoles
  • Transcriptional Activation
  • Up-Regulation

Substances

  • 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