Vorinostat enhances the radiosensitivity of a breast cancer brain metastatic cell line grown in vitro and as intracranial xenografts

摘要: Vorinostat (suberoylanilide hydroxamic acid), a histone deacetylase inhibitor, is currently undergoing clinical evaluation as therapy for cancer. We investigated the effects of vorinostat on tumor cell radiosensitivity in breast cancer brain metastasis model using MDA-MB-231-BR cells. In vitro was evaluated clonogenic assay. Cell cycle distribution and apoptosis measured flow cytometry. DNA damage repair gammaH2AX. Mitotic catastrophe by immunostaining. Growth delay intracranial xenograft models were used to evaluate vivo radiosensitivity. Cells exposed 16 hours before maintained medium after irradiation had an increase with dose enhancement factor 1.57. gammaH2AX, indicator double-strand breaks, significantly more foci per plus group. catastrophe, at 72 hours, increased cells receiving irradiation. Irradiation s.c. tumors mice treated resulted radiation-induced growth delay. Most importantly, animals implants lived longest combination treatment. These results indicate that enhances vivo. There greater than additive improvement survival our model. Combining radiation may be potential treatment option patients who develop metastases.