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

免疫激活 BID 基因放射联合治疗的评估

• 批准号: 23791456
• 负责人: TSUNO Takaya
• 金额: $ 2.66万
• 依托单位: Kansai Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23791456/
• 关键词: BID; アポトーシス; 分子標的療法; 遺伝子治療; IFN-α; 放射線治療

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.

为了克服癌症治疗中的困难，我们已经报道了一项体外研究，即干扰素（IFN）-α在对IFN-α和辐射均具有抗性的A549人肺上皮癌细胞中诱导由BH 3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作用。在BID基因转染的A549裸鼠皮下移植瘤中，IFN-α注射后照射显著抑制肿瘤生长。免疫组化显示，联合治疗导致肿瘤细胞核中BID蛋白的显着减少。电镜下可见联合用药诱导的线粒体凋亡。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甚至对IFN-α和辐射都有抗性的恶性肿瘤。

项目成果

What is a critical factor controlling cell viability regulated by IFN-α?

IFN-α 调节的控制细胞活力的关键因素是什么？

• 发表时间: 2011
• 作者: Morrow AN;Schmeisser H;Tsuno T;Zoon KC.;津野隆哉;Takaya Tsuno;津野隆哉
• 通讯作者: 津野隆哉

BH3 INTERACTING DOMAIN DEATH AGONIST GENE THERAPY ENHANCES ANTITUMOR EFFECT OF INTERFERON-ΑLPHA

BH3 相互作用域死亡激动剂基因治疗增强干扰素-α 的抗肿瘤作用

• 发表时间: 2013
• 作者: Morrow AN;Schmeisser H;Tsuno T;Zoon KC.;津野隆哉
• 通讯作者: 津野隆哉

BH3 INTERACTING DOMAIN DEATH AGONIST GENE THERAPY ENHANCES ANTITUMOR EFFECT OF INTERFERON-ALPHA

BH3 相互作用域死亡激动剂基因治疗增强干扰素-α 的抗肿瘤作用

• 作者: Morrow AN;Schmeisser H;Tsuno T;Zoon KC.;津野隆哉;Takaya Tsuno;津野隆哉;津野 隆哉;Takaya Tsuno
• 通讯作者: Takaya Tsuno