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

Highlights: {yields} The histone deacetylase inhibitor 4-phenylbutyrate substantially enhance efficacy of the receptor tyrosine kinase inhibitors gefitinib or vandetanib in glioma and medulloblastoma cell lines. {yields} Cell death increases and clonogenic survival is reduced in the combination treatments, over mono-therapy. {yields} Combination treatments with these drugs may improve clinical outcome for cancer therapy. -- 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.
Authors:
 [1] ;  [2] ;  [3] ;  [2] ;  [2] ; ;  [4] ;  [3] ;  [2] ;  [1] ;  [2] ;  [1] ;  [2]
  1. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm (Sweden)
  2. (Sweden)
  3. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm (Sweden)
  4. Department of Women's and Children's Health, Karolinska Institutet, Stockholm (Sweden)
Publication Date:
OSTI Identifier:
22207412
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 411; Journal Issue: 1; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; BRAIN; CELL KILLING; CELL PROLIFERATION; DRUGS; GLIOMAS; IN VITRO; RECEPTORS; THERAPY; TUMOR CELLS; TYROSINE