EGFR inhibition using gefitinib is not active in neuroblastoma cell lines

Anticancer Res. 2009 Apr;29(4):1327-33.

Abstract

Background: Inhibition of the epidermal growth factor receptor (EGFR), using a tyrosine kinase inhibitor such as gefitinib, was suggested to be a new treatment approach for neuroblastoma.

Material and methods: EGFR expression and gene mutation were studied by reversetranscriptase-polxmerase chain reacting, fluorescence-activated cell sorting and gene sequencing in six neuroblastoma cell lines. In vitro cytotoxicity of gefitinib 0.1-10 microM alone or in combination with topotecan, vincristine and 9-cis retinoic acid (9cisRA) was determined by MTT proliferation assay.

Results: EGFR overexpression and gene mutations were absent in all cell lines tested. Inhibition of cell viability of 62-85% was found at 10 microM gefitinib, concentrations that, however, can clinically not be reached. In addition, gefitinib increased inhibitory effects of topotecan, vincristine and RA by 10-15% .

Conclusion: Our in vitro data do not support the use of gefitinib as monotherapy in neuroblastoma and its chemosensitizing effects appear minor.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Blotting, Western
  • Cell Proliferation / drug effects
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Flow Cytometry
  • Gefitinib
  • Humans
  • Mutation / genetics
  • Neuroblastoma / drug therapy*
  • Neuroblastoma / metabolism
  • Neuroblastoma / pathology
  • Protein Kinase Inhibitors / pharmacology*
  • Quinazolines / pharmacology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Topotecan / pharmacology
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Quinazolines
  • RNA, Messenger
  • Topotecan
  • ErbB Receptors
  • Gefitinib