Vandetanib alters the protein pattern in malignant glioma and normal brain in the BT4C rat glioma model

Int J Oncol. 2010 Oct;37(4):879-90. doi: 10.3892/ijo_00000739.

Abstract

The treatment of glioblastoma is unsatisfactory. Improved understanding of the biological effects of treatment, together with development of new tools to predict outcome of the initiated treatment are therefore of great need. Vandetanib (ZD6474) is mainly a vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) receptor tyrosine kinase inhibitor. This study investigated the pattern of protein expression in brain tumor and normal brain tissue, following treatment with vandetanib in a rat glioma model. BT4C-cells were stereotactically implanted into the brain of BD IX rats. The rats were divided into three different experiments. The treatment schedule for experiments one and two consisted of daily, oral doses of vandetanib from day 6 until day 12 or 20 after implantation, respectively. In the third experiment, each animal received a single dose of vandetanib on day 19 after implantation and was then sacrificed 2, 8 or 24 h thereafter. The protein expression profiles were analyzed by SELDI-TOF-MS and evaluated with multivariate statistical methods. Following treatment with vandetanib, we found significantly altered protein expression pattern in malignant glioma and normal brain. Analyzing protein spectra is an interesting option to assess biological effects induced in brain tissue by signal transduction inhibitors such as vandetanib.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / pathology
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Drug Administration Schedule
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / metabolism
  • Glioma / drug therapy*
  • Glioma / metabolism
  • Glioma / pathology
  • Multivariate Analysis
  • Nerve Tissue Proteins / metabolism*
  • Piperidines / administration & dosage
  • Piperidines / pharmacology*
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / pharmacology*
  • Proteomics / methods
  • Quinazolines / administration & dosage
  • Quinazolines / pharmacology*
  • Rats
  • Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors
  • Receptors, Vascular Endothelial Growth Factor / metabolism
  • Reproducibility of Results
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Time Factors

Substances

  • Antineoplastic Agents
  • Nerve Tissue Proteins
  • Piperidines
  • Protein Kinase Inhibitors
  • Quinazolines
  • Egfr protein, rat
  • ErbB Receptors
  • Receptors, Vascular Endothelial Growth Factor
  • N-(4-bromo-2-fluorophenyl)-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazolin-4-amine