Lack of interferon beta-induced radiosensitization in four out of five human glioblastoma cell lines

Purpose: To investigate the potential of interferon β to enhance the cytotoxic activity of ionizing irradiation against glioma cells, and to elucidate the possible mechanisms responsible for conflicting clinical results. Methods and Materials: 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 β (n-IFN-β; 30-3000 IU/mL) for 24 h followed by single dose irradiation with 1 to 6 Gy of γ-rays. Results: Significant differences in n-IFN-β sensitivity were found. The cell lines also differed in their radiation sensitivity, and there was no correlation between the n-IFN-β and the radiation sensitivity. In three of five cell lines, the interaction of n-IFN-β and irradiation was infra-additive; in one cell line, it was additive. For MO59J cells only, which are NHEJ-deficient, supra-additivity was observed. Conclusion: Our results confirm the remarkable heterogeneity that is characteristic of malignant glioma. The combined effect of n-IFN-β 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.