Perfluorooctanoic acid stimulates ovarian cancer cell migration, invasion via ERK/NF-κB/MMP-2/-9 pathway

Toxicol Lett. 2018 Sep 15;294:44-50. doi: 10.1016/j.toxlet.2018.05.009. Epub 2018 May 9.

Abstract

As widely used in consumer products, perfluorooctanoic acid (PFOA) has become a common environmental pollutant, which has been detected in human serum and associated with cancers. Our previous study showed that PFOA is a carcinogen that promotes endometrial cancer cell migration and invasion through activation of ERK/mTOR signaling. Here, we showed that PFOA (≥100 nM) treatment also stimulated A2780 ovarian cancer cell invasion and migration, which correlated with increased matrix metalloproteinases MMP-2/-9 expression, important proteases associated with tumor invasion and migration. Notably, PFOA treatment induced activation of ERK1/2/ NF-κB signaling. Pre-treatment with U0126, an ERK1/2inhibitor;or JSH-23, a NF-kB inhibitor, can reverse the PFOA-induced cell migration and invasion. Consistent with these results, inhibiting ERK1/2 or NF-κB signaling abolished PFOA-induced up-regulation of MMP-2/-9 expression. These results indicate that PFOA can stimulate ovarian cancer cell migration, invasion and MMP-2/-9 expression by up-regulating ERK/NF-κB pathway.

Keywords: ERK/NF-κB; MMP-2/-9; Migration and invasion; Ovarian cancer; PFOA.

MeSH terms

  • Active Transport, Cell Nucleus / drug effects
  • Apoptosis / drug effects
  • Butadienes / pharmacology
  • Caprylates / toxicity*
  • Carcinogens, Environmental / toxicity*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Enzyme Induction / drug effects
  • Female
  • Fluorocarbons / toxicity*
  • Humans
  • Kinetics
  • MAP Kinase Signaling System / drug effects*
  • Matrix Metalloproteinase 2 / chemistry
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism*
  • Matrix Metalloproteinase 9 / chemistry
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism*
  • NF-kappa B / agonists*
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism
  • Neoplasm Invasiveness
  • Neoplasm Proteins / agonists
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Nitriles / pharmacology
  • Ovarian Neoplasms / chemically induced*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Phenylenediamines / pharmacology
  • Phosphorylation / drug effects
  • Protein Kinase Inhibitors / pharmacology
  • Protein Processing, Post-Translational / drug effects

Substances

  • 4-methyl-N1-(3-phenylpropyl)benzene-1,2-diamine
  • Butadienes
  • Caprylates
  • Carcinogens, Environmental
  • Fluorocarbons
  • NF-kappa B
  • Neoplasm Proteins
  • Nitriles
  • Phenylenediamines
  • Protein Kinase Inhibitors
  • U 0126
  • perfluorooctanoic acid
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9