Fluvoxamine, an anti-depressant, inhibits human glioblastoma invasion by disrupting actin polymerization

Sci Rep. 2016 Mar 18;6:23372. doi: 10.1038/srep23372.


Glioblastoma multiforme (GBM) is the most common malignant brain tumor with a median survival time about one year. Invasion of GBM cells into normal brain is the major cause of poor prognosis and requires dynamic reorganization of the actin cytoskeleton, which includes lamellipodial protrusions, focal adhesions, and stress fibers at the leading edge of GBM. Therefore, we hypothesized that inhibitors of actin polymerization can suppress GBM migration and invasion. First, we adopted a drug repositioning system for screening with a pyrene-actin-based actin polymerization assay and identified fluvoxamine, a clinically used antidepressant. Fluvoxamine, selective serotonin reuptake inhibitor, was a potent inhibitor of actin polymerization and confirmed as drug penetration through the blood-brain barrier (BBB) and accumulation of whole brain including brain tumor with no drug toxicity. Fluvoxamine inhibited serum-induced ruffle formation, cell migration, and invasion of human GBM and glioma stem cells in vitro by suppressing both FAK and Akt/mammalian target of rapamycin signaling. Daily treatment of athymic mice bearing human glioma-initiating cells with fluvoxamine blocked tumor cell invasion and prolonged the survival with almost same dose of anti-depressant effect. In conclusion, fluvoxamine is a promising anti-invasive treatment against GBM with reliable approach.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / metabolism
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Dose-Response Relationship, Drug
  • Drug Repositioning
  • Fluvoxamine / administration & dosage*
  • Fluvoxamine / pharmacology
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glioblastoma / drug therapy*
  • Glioblastoma / metabolism
  • Humans
  • Mice
  • Neoplasm Invasiveness
  • Neoplastic Stem Cells / drug effects*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects
  • Survival Analysis
  • TOR Serine-Threonine Kinases / metabolism*
  • Treatment Outcome
  • Xenograft Model Antitumor Assays


  • TOR Serine-Threonine Kinases
  • Focal Adhesion Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-akt
  • Fluvoxamine