title: Livin modulates the apoptotic effects of vesicular stomatotitis virus in lung adenocarcinoma.
abstract: Vesicular stomatitis virus (VSV) has shown promise in cancer treatment. However, it achieved limited effects against lung cancer. Lung cancer has intrinsic mechanisms that render resistance to VSV. In this study, we attempted to explore the expression of the anti-apoptotic factor Livin in lung adenocarcinoma and its possible relationship to VSV vulnerability. We found VSV induced apoptosis in a time- and dose-dependent manner, with the concomitant change in the expression of Livin. We elevated the expression of Livin both transiently and stably, and the cells became insensitive to VSV treatment. We further found the BIR domain of Livin was mainly responsible for its modulation effects. This finding suggested a possible interaction with the second mitochondria-derived activator of caspase (SMAC). The knock-down of SMAC also inhibited apoptosis by VSV. The relationship was confirmed by the co-immunoprecipitation. Finally, we knocked down the endogenous Livin, and the knock-down sensitized cells to VSV treatment. Our results suggested the important role of Livin and its partner molecule in the process of VSV treatment.
authors.affiliation: Division of Thoracic Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, P.R. China.
authors.forename: Gui-Hong
authors.initials: GH
authors.lastname: Liu
authors.affiliation: Department of Oncology, Chengdu First People's Hospital, Chengdu 610041, P.R. China.
authors.forename: Wei-Lin
authors.initials: WL
authors.lastname: Wang
authors.affiliation: Division of Endocrinology and Metabolism, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, P.R. China.
authors.forename: Chun
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Oncology, Chengdu First People's Hospital, Chengdu 610041, P.R. China.
authors.forename: Chang-Lin
authors.initials: CL
authors.lastname: Li
authors.affiliation: Division of Abdominal Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, P.R. China.
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Zhang
authors.affiliation: Division of Abdominal Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, P.R. China.
authors.forename: Qiu
authors.initials: Q
authors.lastname: Li
authors.affiliation: Division of Thoracic Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, P.R. China.
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Ding
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000230:Adenocarcinoma / Q000235:genetics / Q000628:therapy* / Q000821:virology; D000077192:Adenocarcinoma of Lung; D017209:Apoptosis / Q000235:genetics; D053148:Caspase 3 / Q000235:genetics; D045744:Cell Line, Tumor; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics / Q000628:therapy* / Q000821:virology; D009363:Neoplasm Proteins / Q000235:genetics*; D050130:Oncolytic Virotherapy; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C419866:BIRC7 protein, human; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D053148:Caspase 3