Danthron inhibits the migration and invasion of human brain glioblastoma multiforme cells through the inhibition of mRNA expression of focal adhesion kinase, Rho kinases-1 and metalloproteinase-9

Oncol Rep. 2009 Nov;22(5):1033-7. doi: 10.3892/or_00000532.

Abstract

In this study, we investigated the effect of danthron on the cell migration and invasion of human brain glioblastoma multiforme GBM 8401 cells in vitro. The changes of migration and invasion of GBM 8401 cells after treatment with danthron were detected by cell migration assay and cell invasion assay. The levels of mRNA gene expression associated with cell migration and invasion were detected by real-time PCR. Results indicated that human brain glioblastoma multiforme GBM 8401 cells treated with danthron in vitro migrated and invaded less than cells treated with phosphate-buffered saline (PBS) (control). Western blotting showed that danthron inhibited the protein levels of FAK, MMP-7, MMP-9 and uPA in GBM 8401 cells. Real-time PCR assay also showed that danthron inhibited the mRNA expression of matrix metalloproteinase-9 (MMP-9), FAK and ROCK-1 of GBM 8401 cells. These results showed that danthron inhibited invasion and migration of GBM 8401 cells by downregulating mRNA expression associated with these processes, resulting in reduced metastasis. Thus, danthron may be considered a therapeutic agent that can inhibit primary tumor growth and prevent metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anthraquinones / pharmacology*
  • Blotting, Western
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology
  • Cell Adhesion / drug effects
  • Cell Movement / drug effects*
  • Focal Adhesion Kinase 1 / genetics*
  • Focal Adhesion Kinase 1 / metabolism
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Glioblastoma / drug therapy*
  • Glioblastoma / genetics
  • Glioblastoma / pathology
  • Humans
  • Matrix Metalloproteinase 9 / genetics*
  • Matrix Metalloproteinase 9 / metabolism
  • Mutagens / pharmacology
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured
  • rho-Associated Kinases / genetics*
  • rho-Associated Kinases / metabolism

Substances

  • Anthraquinones
  • Mutagens
  • RNA, Messenger
  • Focal Adhesion Kinase 1
  • PTK2 protein, human
  • rho-Associated Kinases
  • Matrix Metalloproteinase 9
  • danthron