SU11657 enhances radiosensitivity of human meningioma cells.
OBJECTIVE
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
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.


CONCLUSIONS
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.
Milker-Zabel
Stefanie
S
Department of Radiation Oncology, University of Heidelberg, Heidelberg, Germany. stefanie_milker-zabel@med.uni-heidelberg.de
Zabel-du Bois
Angelika
A
Ranai
Gholamreza
G
Trinh
Thuy
T
Unterberg
Andreas
A
Debus
Jürgen
J
Lipson
Kenneth E
KE
Abdollahi
Amir
A
Huber
Peter E
PE
D054443:Cell Migration Assays / Q000379:methods; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008577:Meningeal Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D008579:Meningioma / Q000098:blood supply / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D009363:Neoplasm Proteins / Q000378:metabolism; D009930:Organic Chemicals / Q000494:pharmacology*; D011836:Radiation Tolerance / Q000187:drug effects*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism
D009363:Neoplasm Proteins; D009930:Organic Chemicals; C474557:SU 11657; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases