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

为了克服癌症治疗的困难，我们报道了一项体外研究，干扰素(IFN)- α诱导对IFN- α和辐照均耐药的A549人肺上皮癌细胞中由bh3相互作用结构域死亡激动剂（BID）介导的线粒体凋亡（Tsuno T, et al, 2012）。在这里，我们进一步评估了ifn - α激活的BID基因治疗联合放射治疗的体内抗肿瘤效果。转染BID基因的A549异种移植物皮下接种裸鼠后，ifn - α注射后辐照显著抑制肿瘤生长。免疫组化显示，联合治疗导致肿瘤细胞核中BID蛋白显著降低。电镜观察显示联合治疗诱导线粒体凋亡。因此，联合治疗显示出显著的抗肿瘤作用，表明它可能有希望治疗恶性肿瘤，甚至对ifn - α和照射都有抗药性。

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.