Lack of interferon beta-induced radiosensitization in four out of five human glioblastoma cell lines.
OBJECTIVE
To investigate the potential of interferon beta to enhance the cytotoxic activity of ionizing irradiation against glioma cells, and to elucidate the possible mechanisms responsible for conflicting clinical results.


METHODS
Five glioblastoma cell lines (U87MG, U118MG, U373MG, MO59K, MO59J) with different radiosensitivity and genetic background were used. Experiments were performed in exponentially growing cultures, and cell survival was measured by a colony-forming assay. Cells were incubated with natural interferon beta (n-IFN-beta; 30-3000 IU/mL) for 24 h followed by single dose irradiation with 1 to 6 Gy of gamma-rays.


RESULTS
Significant differences in n-IFN-beta sensitivity were found. The cell lines also differed in their radiation sensitivity, and there was no correlation between the n-IFN-beta and the radiation sensitivity. In three of five cell lines, the interaction of n-IFN-beta and irradiation was infra-additive; in one cell line, it was additive. For MO59J cells only, which are NHEJ-deficient, supra-additivity was observed.


CONCLUSIONS
Our results confirm the remarkable heterogeneity that is characteristic of malignant glioma. The combined effect of n-IFN-beta and radiation was mostly infra-additive or additive; synergistic interaction might occur in tumor cells that already have acquired repair deficiencies because of their genetic instability, as shown for the MO59J cell line.
Schmidberger
Heinz
H
Department of Radiation Oncology, Georg-August Universität Göttingen, Göttingen, Germany. hschmbg@med.unigoettingen.de
Rave-Fränk
Margret
M
Lehmann J
Jörg
J
Weiss
Elisabeth
E
Gerl
Lara
L
Dettmer
Nadine
N
Glomme
Sabine
S
Hess
C F
CF
D000730:Androstadienes / Q000494:pharmacology; D001932:Brain Neoplasms / Q000473:pathology*; D004260:DNA Repair; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D004307:Dose-Response Relationship, Radiation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D009687:Nuclear Proteins; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D011836:Radiation Tolerance; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects; D014410:Tumor Stem Cell Assay; D000077191:Wortmannin
D000730:Androstadienes; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D016899:Interferon-beta; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011838:Radiation-Sensitizing Agents; D000077191:Wortmannin; C497263:PRKDC protein, human