title: Silencing of Livin inhibits tumorigenesis and metastasis via VEGF and MMPs pathway in lung cancer.
abstract: Livin, an inhibitor of apoptosis protein (IAP), is overexpressed in various cancers and decreases tumor sensitivity to chemotherapy and radiotherapy. However, the effect of Livin on lung adenocarcinoma metastasis and the specific mechanism involved remain unclear. RNAi technology was used to stably silence Livin in A549 cells in the present study. The effect of Livin on tumor growth and invasion was investigated in lung cancer cells in vitro and animal models were established to determine the anti-metastasis ability of Livin silencing in vivo. The results indicated that Livin knock-down suppressed cell proliferation and inhibited cell invasion, accompanied by downregulation of VEGF and MMP-2/-9. Silencing of Livin resulted in the prevention of xenograft tumor formation. Seventy-five immunodeficient male BALB/C nude mice were randomly divided into three groups, the relative ratio of the areas with pulmonary nodules in the experimental group decreased from 46.71±7.27% to 11.07±2.94% compared with the negative control group (P<0.001), indicating the interaction between Livin, VEGF and MMPs. The xenograft tumor model of intravenous injection of tumor cells were successfully established and applied for the analysis of lung cancer tumorigenesis and metastasis in a time-dependent manner for the first time. Based on the reliable and reproducible animal model, our findings indicate that knock-down of Livin inhibits cell growth and invasion through blockade of the VEGF and MMPs pathways in lung cancer cells in vitro, and inhibits tumorigenesis and metastasis of lung cancer in vivo, suggesting that Livin is a promising antitumor target.
authors.affiliation: Department of Respiratory Medicine, Fujian Provincial Hospital, Fujian Provincial Clinical Medical College of Fujian Medical University, Fuzhou 350001, P.R. China.
authors.forename: Xian
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Respiratory Medicine, Fujian Provincial Hospital, Fujian Provincial Clinical Medical College of Fujian Medical University, Fuzhou 350001, P.R. China.
authors.forename: Hong-Ru
authors.initials: HR
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, Fujian Zhangzhou First Hospital, Clinical Medical College of Fujian Medical University, Zhangzhou 363000, P.R. China.
authors.forename: Xiao-Fen
authors.initials: XF
authors.lastname: Lin
authors.affiliation: Department of Respiratory Medicine, Fujian Provincial Hospital, Fujian Provincial Clinical Medical College of Fujian Medical University, Fuzhou 350001, P.R. China.
authors.forename: Mei-E
authors.initials: ME
authors.lastname: Yu
authors.affiliation: Department of Respiratory Medicine, Fujian Provincial Hospital, Fujian Provincial Clinical Medical College of Fujian Medical University, Fuzhou 350001, P.R. China.
authors.forename: Xun-Wei
authors.initials: XW
authors.lastname: Tu
authors.affiliation: Department of Respiratory Medicine, Fujian Provincial Hospital, Fujian Provincial Clinical Medical College of Fujian Medical University, Fuzhou 350001, P.R. China.
authors.forename: Zhi-Dan
authors.initials: ZD
authors.lastname: Hua
authors.affiliation: Department of Respiratory Medicine, Fujian Provincial Hospital, Fujian Provincial Clinical Medical College of Fujian Medical University, Fuzhou 350001, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Lin
authors.affiliation: Department of Respiratory Medicine, Fujian Provincial Hospital, Fujian Provincial Clinical Medical College of Fujian Medical University, Fuzhou 350001, P.R. China.
authors.forename: Neng-Luan
authors.initials: NL
authors.lastname: Xu
authors.affiliation: Cardiovascular Key Laboratory of Fujian Province, Fujian Provincial Hospital, Fujian Provincial Clinical Medical College of Fujian Medical University, Fuzhou 350001, P.R. China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Han
authors.affiliation: Department of Respiratory Medicine, Fujian Provincial Hospital, Fujian Provincial Clinical Medical College of Fujian Medical University, Fuzhou 350001, P.R. China.
authors.forename: Yu-Sheng
authors.initials: YS
authors.lastname: Chen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009368:Neoplasm Transplantation; D034622:RNA Interference; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C419866:BIRC7 protein, human; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C000607735:livin protein, mouse; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9