Evaluation of combination effects of 2- methoxyestradiol and methoxyamine on IUdR inducedradiosensitization in glioma spheroids

Background: Glioblastoma is the most common and most malignant cancer of central nervous system. Targeted radiotherapy is an effective method toward its treatment. Iododeoxyuridine (IUdR) is a halogenated thymidine analogue known to be effective as a radiosensitizer in human cancer therapy. In this study we have evaluated the combina- tion effects of 2-Methoxyestradiol, an inhibitor of hypoxia inducible factor 1ƒ¿ (HIF-1ƒ¿) and Methoxyaminem, an inhibitor of base excision repair (BER) pathway on radiosensitization of IUdR in glioblastoma spheroid culture. Materials and Methods: The cytotoxic damages of DNA in U87MG cell line were compared using colony formation assay. Experiments were performed in large spheroids with a diameter of approximately 350ƒÊm. Results: Evaluation of the effects of IUdR with 2ME2 and MX pretreatment on spheroid cultured cell followed by ionizing irradiation showed more enhancemented (p.0.001) IUdR induced-radiosensitization. These results introduced a key role for 2ME2 in IUdR related studies. Conclusion: Pretreatment of tumor cells with IUdR, MX and 2ME2 before irradiation enhances tumor radiosensitization and may improve therapeu- tic index for IUdR and 2ME2.