FTY720 reduces migration and invasion of human glioblastoma cell lines via inhibiting the PI3K/AKT/mTOR/p70S6K signaling pathway

Tumour Biol. 2014 Nov;35(11):10707-14. doi: 10.1007/s13277-014-2386-y. Epub 2014 Jul 30.

Abstract

2-Amino-2-[2-(4-octylphenyl)]-1,3-propanediol hydrochloride (FTY720), a synthetic compound from Isaria sinclairii, has been proven to possess various biological benefits including anti-cancer activity. However, the effects and related mechanisms of FTY720 on the migration and invasion of glioblastoma cells are still unclear. In the present study, we utilized U251MG and U87MG human glioblastoma cell lines to assess the effects of FTY720. We found that FTY720 significantly inhibited migration and invasion of glioblastoma cells. The anti-migration and invasion effects of FTY720 were associated with its down-regulation of matrix metalloproteinase-2 (MMP-2) and MMP-9 while up-regulation of tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2. Furthermore, FTY720 modulated the expression of roundabouts 1 (ROBO1), Rho-associated kinase-1 (ROCK1), and epithelial-to-mesenchymal transition (EMT)-related factors. In addition, the phosphatidylinositide 3-kinases/protein kinase B/mammalian target of rapamycin/p70S6 kinase (PI3K/AKT/mTOR/p70S6K) signaling pathway participated in FTY720-mediated suppression of migration and invasion. Thus, our findings demonstrated that FTY720 reduced glioblastoma cells migration and invasion via multiple signaling pathways, suggesting that FTY720 is a potential therapeutic agent against glioblastoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Blotting, Western
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects
  • Fingolimod Hydrochloride
  • Glioblastoma / drug therapy*
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Neoplasm Invasiveness
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors*
  • Propylene Glycols / pharmacology*
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Ribosomal Protein S6 Kinases, 70-kDa / antagonists & inhibitors*
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism
  • Signal Transduction / drug effects
  • Sphingosine / analogs & derivatives*
  • Sphingosine / pharmacology
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*
  • TOR Serine-Threonine Kinases / metabolism
  • Tumor Cells, Cultured
  • Wound Healing / drug effects

Substances

  • Immunosuppressive Agents
  • Phosphoinositide-3 Kinase Inhibitors
  • Propylene Glycols
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Ribosomal Protein S6 Kinases, 70-kDa
  • Fingolimod Hydrochloride
  • Sphingosine