Basic research in molecular targeting therapy of malignant gliomas against NF-kB

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It has been reported that NF-kB (nudear factor-kB) is a transcription factor, which controls cell proliferation of many kinds of cancer cells. This factor in inactive form is translocated in the cytoplasm and once activated by radiation or chemotherapeutic agent, NF-kB translocates into nucleus to prevent apoptosis. The authors previously reported that NF-kB is constitutively activated in malignant glioma cells, and inhibition of NF-kB resulted in the growth inhibition of the cultured human glioma cells. Therefore, the authors assume that NF-kB is the potential molecular target in the treatment strategy of malignant gliomas.This study investigated the relationship between the immunohistochemical finding of activated NF-kB and Mib-1 staining index using human glioma specimin. In addition, change of the radiation sensitivity of malignant glioma cell line (A172) by anti-NF-kB drug (pitavastatin) was analysed using MTT assay. The presence of activated form of NF-kB was confirmed by nuclear … More localization in all glioma specimin. Normal brain tissue was negative for activated form of NF-kB. Intensity of the activated form of NF-kB staining was correlated with Mib-1 staining index. This finding suggested that constitutive activation of NF-kB in gliomas were associated with growth potential. Radiation sensitivity of cultured glioma cell line (A172) was enhanced by anti-NF-kB (pitavastatin) pretreatment Pitavastatin at the concentration of 100μM was not inhibitory to A172 cells in monolayer culture, but it enhanced radiation sensitivity of A172 cells by MTT assay. Sensitization enhancement ratio was 5. Immunoblotting of the activated form of NF-kB (p50) was performed using nuclear rich lysate of cultured A172 cells. Activated form of NF-kB (p50) rapid ly increased in control A172 cells ater exposure to 15Gy radiation. However, pretreatment of A172 cells at the concentration of 100μM resulted in no increase of the activated form of NF-kB (p50). This finding may be important in the mechanism of radiosensitization of glioma cells by anti-NF-kB drug pitavastatin.In conclusion, our study demonstrate that NF-kB is constitutively activated in all of the glioma cells. Inhibition of N-kB is effective both inhibiting glioma growth and rasiosensitization of glioma cells. Therefore, NF-kB is potential molecular target to establish the new treatment strategy for malignant gliomas. Less