Enhanced effects by 4-phenylbutyrate in combination with RTK inhibitors on proliferation in brain tumor cell models

Biochem Biophys Res Commun. 2011 Jul 22;411(1):208-12. doi: 10.1016/j.bbrc.2011.06.141. Epub 2011 Jun 25.

Abstract

We have investigated in vitro effects of anticancer therapy with the histone deacetylase inhibitor (HDACi) 4-phenylbutyrate (4-PB) combined with receptor tyrosine kinase inhibitors (RTKi) gefitinib or vandetanib on the survival of glioblastoma (U343MGa) and medulloblastoma (D324Med) cells. In comparison with individual effects of these drugs, combined treatment with gefitinib/4-PB or vandetanib/4-PB resulted in enhanced cell killing and reduced clonogenic survival in both cell lines. Our results suggest that combined treatment using HDACi and RTKi may beneficially affect the outcome of cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Brain Neoplasms / enzymology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Gefitinib
  • Glioblastoma / enzymology*
  • Histone Deacetylase Inhibitors / pharmacology*
  • Humans
  • Models, Biological
  • Phenylbutyrates / pharmacology*
  • Piperidines / pharmacology
  • Protein Kinase Inhibitors / pharmacology*
  • Quinazolines / pharmacology
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Tumor Stem Cell Assay

Substances

  • Histone Deacetylase Inhibitors
  • Phenylbutyrates
  • Piperidines
  • Protein Kinase Inhibitors
  • Quinazolines
  • 4-phenylbutyric acid
  • Receptor Protein-Tyrosine Kinases
  • Gefitinib
  • vandetanib