SU11657 enhances radiosensitivity of human meningioma cells

Int J Radiat Oncol Biol Phys. 2008 Mar 15;70(4):1213-8. doi: 10.1016/j.ijrobp.2007.11.041. Epub 2008 Jan 30.


Purpose: To analyze the effect of the multireceptor tyrosine kinase inhibitor SU11657 (primarily vascular endothelial growth factor, platelet-derived growth factor) in combination with irradiation in freshly isolated primary human meningioma cells.

Methods and materials: Tumor specimens were obtained from meningioma patients undergoing surgery at the Department of Neurosurgery, University of Heidelberg, Germany. For the present study only cells up to passage 6 were used. Benign and atypical meningioma cells and human umbilical vein endothelial cells (HUVEC) were treated with SU11657 alone and in combination with 6-MV photons (0-10 Gy). Clonogenic survival and cell proliferation were determined alone and in coculture assays to determine direct and paracrine effects.

Results: Radiation and SU11657 alone reduced cell proliferation in atypical and benign meningioma cells as well as in HUVEC in a dose-dependent manner. SU11657 alone also reduced clonogenic survival of benign and atypical meningioma cells. SU11657 increased radiosensitivity of human meningioma cells in clonogenic survival and cell number/proliferation assays. The anticlonogenic and antiproliferative effects alone and the radiosensitization effects of SU11657 were more pronounced in atypical meningioma cells compared with benign meningioma cells.

Conclusion: Small-molecule tyrosine kinase inhibitors like SU11657 are capable of amplifying the growth inhibitory effects of irradiation in meningioma cells. These data provide a rationale for further clinical evaluation of this combination concept, especially in atypical and malignant meningioma patients.

MeSH terms

  • Cell Migration Assays / methods
  • Cell Proliferation / drug effects
  • Cell Proliferation / radiation effects
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Meningeal Neoplasms / blood supply
  • Meningeal Neoplasms / metabolism
  • Meningeal Neoplasms / pathology
  • Meningeal Neoplasms / radiotherapy*
  • Meningioma / blood supply
  • Meningioma / metabolism
  • Meningioma / pathology
  • Meningioma / radiotherapy*
  • Neoplasm Proteins / metabolism
  • Organic Chemicals / pharmacology*
  • Radiation Tolerance / drug effects*
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Umbilical Veins / cytology
  • Umbilical Veins / drug effects
  • Vascular Endothelial Growth Factors / metabolism


  • Neoplasm Proteins
  • Organic Chemicals
  • SU 11657
  • Vascular Endothelial Growth Factors
  • Receptor Protein-Tyrosine Kinases