title: Inhibition of invasion and metastasis of MHCC97H cells by expression of snake venom cystatin through reduction of proteinases activity and epithelial-mesenchymal transition.
abstract: Snake venom cystatin (sv-cystatin) is a member of the cystatin family of cysteine protease inhibitors. To further evaluate the possibility of sv-cystatin in cancer therapy, this study examined the effects of sv-cystatin on the invasion and metastasis of liver cancer cells (MHCC97H) in vitro and in vivo as well as the underlying mechanism. sv-cystatin cDNA was transfected into MHCC97H cells and the anti-invasion and antimetastasis effects of sv-cystatin were determined using migration and matrigel invasion assays and a lung-metastasis mice model. The results suggest that sv-cyst clone (sv-cystatin expression in MHCC97H cells) delayed the invasion and metastasis in vitro and in vivo compared to the parental, mock and si-sv-cyst clone cells (inhibited sv-cystatin expression by siRNA). The decreased activities of cathepsin B, MMP-2 and MMP-9 and EMT change index including higher E-cadherin, lower N-cadherin and decreased Twist activity were observed in the sv-cyst clone, which contributes to the change in invasion and metastasis ability of MHCC97H cells. This study provides evidence that expression of the sv-cystatin gene in MHCC97H cells inhibits tumor cell invasion and metastasis through the reduction of the proteinases activity and Epithelial-Mesenchymal Transition (EMT), which might contribute to the anticancer research of the sv-cystatin protein.
authors.affiliation: Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Research Center for Molecular Medicine, Fujian Medical University, Fuzhou 350004, China.
authors.forename: Nanhong
authors.initials: N
authors.lastname: Tang
authors.forename: Qun
authors.initials: Q
authors.lastname: Xie
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Wang
authors.forename: Xiujin
authors.initials: X
authors.lastname: Li
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Chen
authors.forename: Xu
authors.initials: X
authors.lastname: Lin
authors.forename: Jianyin
authors.initials: J
authors.lastname: Lin
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D002401:Cathepsin B / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002999:Clone Cells; D015891:Cystatins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D018093:Gelatinases / Q000378:metabolism*; D020868:Gene Silencing; D015316:Genetic Therapy; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control / Q000556:secondary; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009687:Nuclear Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D012910:Snake Venoms / Q000378:metabolism*; D051879:Twist-Related Protein 1 / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D015891:Cystatins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012910:Snake Venoms; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; C533912:CTSB protein, human; D002401:Cathepsin B; D018093:Gelatinases