evaluation of combination effects of 2- methoxyestradiol and methoxyamine on iudrinduced radiosensitization 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 combination effects of 2-methoxyestradiol, an inhibitor of hypoxia inducible factor 1α (hif-1α) 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 350μm. 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 therapeutic index for iudr and 2me2. iran. j. radiat. res., 2010 7 (4): 211-216