Tamoxifen radiosensitization in human glioblastoma cell lines

Object. A combined tamoxifen and radiation therapy is being used in clinica l trials to treat glioblastoma multiforme (GBM). The rationale behind this therapy is that tamoxifen is a radiosensitizer. However. the evidence for t his is weak. The authors, therefore, examined the effect of combined radiat ion-tamoxifen therapy in three GEM cell lines of human origin. Methods. The GEM cell lines were exposed to different concentrations (0.3-5 mu g/ml) of tamoxifen and subsequently irradiated at varying doses (0.8-5 Gy). Tumor growth inhibition was measured using a proliferation assay. The interaction of tamoxifen and radiation therapies was quantified using the c ombination index method, which distinguishes whether a combined antitumor e ffect is synergistic, additive, or antagonistic. At high doses of tamoxifen or radiation there was significant inhibition of tumor cell proliferation. At low doses of either therapeutic agent, there was little effect. In one cell line, synergism occurred at high doses of tamoxifen and radiation. In the other two cell lines, an additive effect was observed. In only one of t he three cell lines was there synergy between tamoxifen and radiation at do ses that significantly inhibited tumor proliferation. Conclusions. Because synergy could not be demonstrated in all three cell li nes at active dosages, the clinical combination of tamoxifen and radiation therapies may not be of benefit to all patients.