Assessment of immune-activated BID gene-radiation combined modality therapy

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To overcome difficulties in cancer therapy, we have reported an in vitro study that interferon (IFN)-alpha induces mitochondrial apoptosis mediated by BH3-interacting domain death agonist (BID) in A549 human lung epithelial carcinoma cells resistant to both IFN-alpha and irradiation (Tsuno T, et al, 2012). Here, we further assessed in vivo antitumor effects of IFN-alpha-activated BID gene therapy combined with radiation therapy. In BID gene transfected A549 xenografts inoculated subcutaneously into nude mice, IFN-alpha injection followed by irradiation remarkably inhibited tumor growth. Immunohistochemistry revealed that the combined therapy led to dramatic reduction in BID protein in the nuclei of tumor cells. Electron micrographs disclosed mitochondrial apoptosis induced by the combined therapy. Thus, the combined modality therapy exhibited notable antitumor effects, suggesting that it may be promising to treat malignant tumors even resistant to both IFN-alpha and irradiation.