Zoledronic acid inhibits proliferation and impairs migration and invasion through downregulating VEGF and MMPs expression in human nasopharyngeal carcinoma cells

Med Oncol. 2012 Jun;29(2):714-20. doi: 10.1007/s12032-011-9904-1. Epub 2011 Mar 24.

Abstract

To demonstrate the effect of zoledronic acid in proliferation, invasion, and migration of human nasopharyngeal carcinoma cell HNE-1 and explore the potential role of VEGF, MMP-2, and MMP-9 proteins in vitro. Human nasopharyngeal carcinoma cell HNE-1 was exposed to various concentrations (0-40 μmol/l) of zoledronic acid. Zoledronic acid inhibited proliferation of HNE-1 cells though not in a dose-dependent manner. Zoledronic acid had exerted a dose-dependent effect on the migration and invasion of HNE-1 cells. Both expressions of mRNA and protein of MMP2, MMP9, and VEGF were reduced, respectively, detected by RT-PCR and Western blot assays. These data suggested that zoledronic acid not only inhibited growth but also invasion and migration of HNE-1 cells in vitro. The anti-cancer action of zoledronic acid was partially associated with the suppression of VEGF expression and secretion and downregulating the expression of MMP2 and MMP9.

MeSH terms

  • Blotting, Western
  • Bone Density Conservation Agents / pharmacology*
  • Carcinoma
  • Cell Adhesion / drug effects
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects*
  • Diphosphonates / pharmacology*
  • Down-Regulation
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Imidazoles / pharmacology*
  • Matrix Metalloproteinase 2 / genetics*
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics*
  • Matrix Metalloproteinase 9 / metabolism
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / genetics
  • Nasopharyngeal Neoplasms / metabolism*
  • Nasopharyngeal Neoplasms / pathology*
  • Neoplasm Invasiveness
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor A / genetics*
  • Vascular Endothelial Growth Factor A / metabolism
  • Zoledronic Acid

Substances

  • Bone Density Conservation Agents
  • Diphosphonates
  • Imidazoles
  • RNA, Messenger
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Zoledronic Acid
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9