Trail armed oncolytic poxvirus suppresses lung cancer cell by inducing apoptosis  

作　　者：Jinqing Hu Huaiyuan Wang Jinfa Gu Xinyuan Liu Xiumei Zhou 

机构地区：[1]Laboratory of Cell Biology, Xin-yuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, China [2]State Key Laboratory of Cell Biology, Innovation Center for Cell Signaling Network, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China

出　　处：《Acta Biochimica et Biophysica Sinica》2018年第10期1018-1027,共10页生物化学与生物物理学报（英文版）

基　　金：This work was supported the grants from a Program of the Conba-Zhejiang Sci-Tech University, Academician Workstation （No. 116129A4J14365）, the National Natural Science Foundation of China （Nos. 81372453 and 81572999）, Shanghai Institutes for Biological Science, Chinese Academy of Sciences, and Sichuan Huiyang Life Science and Technology Corp. Research Program （No. Y363S21763）.

摘　　要：Lung cancer has a high morbidity rate worldwide and is often resistant to therapy. Oncolytic virus therapy is a developing trend for cancer treatment. Thus, we constructed an oncolytic poxvirus carrying human trail gene that expresses a membrane-binding tumor necrosis factor and associated apoptosis-inducing ligand （TRAIL, Onco^pox-trail）. We hypothesized that the expression of trail would increase the efficacy of the oncolytic poxvirus. The effect of the TRAIL protein depends on the death receptors on the surface of different cancer cells. The expression of death receptors in lung cancer cell lines was analyzed by western blot analysis. In vitro, the oncolytic poxvirus carrying the trail gene displayed a better cytotoxicity at the cell level in the lung cancer cell line than that carrying the Onco^pox-empty. TRAIL protein mainly induced apoptosis and inhibited necrosis. In vivo, two transplanted tumor models of human A549 lung cancer cells and mouse Lewis lung cancer cells were used to verify the anti-cancer effect of the oncolytic poxvirus carrying the trail gene. TUNEL staining results of the tumor histological sections also verified the anti-cancer effect. Similarly, through systemic administration of Onco^pox-trail, the oncolytic poxvirus also exhibited anti-cancer effect.Lung cancer has a high morbidity rate worldwide and is often resistant to therapy. Oncolytic virus therapy is a developing trend for cancer treatment. Thus, we constructed an oncolytic poxvirus carrying human trail gene that expresses a membrane-binding tumor necrosis factor and associated apoptosis-inducing ligand （TRAIL, Onco^pox-trail）. We hypothesized that the expression of trail would increase the efficacy of the oncolytic poxvirus. The effect of the TRAIL protein depends on the death receptors on the surface of different cancer cells. The expression of death receptors in lung cancer cell lines was analyzed by western blot analysis. In vitro, the oncolytic poxvirus carrying the trail gene displayed a better cytotoxicity at the cell level in the lung cancer cell line than that carrying the Onco^pox-empty. TRAIL protein mainly induced apoptosis and inhibited necrosis. In vivo, two transplanted tumor models of human A549 lung cancer cells and mouse Lewis lung cancer cells were used to verify the anti-cancer effect of the oncolytic poxvirus carrying the trail gene. TUNEL staining results of the tumor histological sections also verified the anti-cancer effect. Similarly, through systemic administration of Onco^pox-trail, the oncolytic poxvirus also exhibited anti-cancer effect.

关 键 词：oncolytic poxvirus TRAIL protein APOPTOSIS lung cancer 

分 类 号：Q513.2[生物学—生物化学] X503.2[环境科学与工程—环境工程]