Evaluation of combination effects of 2- methoxyestradiol and methoxyamine on IUdRinduced radiosensitization in glioma spheroids

ABSTRACT

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 combination effects of 2-Methoxyestradiol, an inhibitor of hypoxia inducible factor 1 alpha [HIF-1 alpha] and Methoxyaminem, an inhibitor of base excision repair [BER] pathway on radiosensitization of IUdR in glioblastoma spheroid culture. 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 350micro m. Evaluation of the effects of IUdR with 2ME2 and MX pretreatment on spheroid cultured cell followed by ionizing irradiation showed more enhancemented [p IUdR induced-radiosensitization. These results introduced a key role for 2ME2 in IUdR related studies. Pretreatment of tumor cells with IUdR, MX and 2ME2 before irradiation enhances tumor radiosensitization and may improve therapeutic index for IUdR and 2ME2