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: Nanhong Tang, Qun Xie, Xiaoqian Wang, Xiujin Li, Yanlin Chen, Xu Lin, Jianyin Lin
• Journal: Archives of pharmacal research (Arch Pharm Res) Vol. 34 Issue 5 Pg. 781-9 (May 2011) ISSN: 1976-3786 [Electronic] Korea (South)
• PMID: 21656364 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cystatins
• Nuclear Proteins
• RNA, Messenger
• RNA, Small Interfering
• Snake Venoms
• TWIST1 protein, human
• Twist-Related Protein 1
• CTSB protein, human
• Cathepsin B
• Gelatinases

Topics

• Animals
• Carcinoma, Hepatocellular (metabolism, pathology, secondary, therapy)
• Cathepsin B (metabolism)
• Cell Line, Tumor
• Cell Movement
• Clone Cells
• Cystatins (antagonists & inhibitors, genetics, metabolism)
• Epithelial-Mesenchymal Transition
• Gelatinases (metabolism)
• Gene Silencing
• Genetic Therapy
• Liver Neoplasms (metabolism, pathology, therapy)
• Lung Neoplasms (metabolism, pathology, prevention & control, secondary)
• Male
• Mice
• Mice, Nude
• Neoplasm Invasiveness (prevention & control)
• Nuclear Proteins (metabolism)
• RNA, Messenger (metabolism)
• RNA, Small Interfering
• Snake Venoms (metabolism)
• Twist-Related Protein 1 (metabolism)
• Xenograft Model Antitumor Assays