2013 Fiscal Year Final Research Report

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

Research Project

Project/Area Number	23791456
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Radiation science
Research Institution	Kansai Medical University
Principal Investigator	TSUNO Takaya 関西医科大学, 医学部, 助教 (60598259)
Project Period (FY)	2011 – 2013
Keywords	BID / アポトーシス / 分子標的療法 / 遺伝子治療
Research Abstract	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.