title: Selection of peptide inhibitor to matrix metalloproteinase-2 using phage display and its effects on pancreatic cancer cell lines PANC-1 and CFPAC-1.
abstract: Despite tremendous advances in cancer treatment and survival rates, pancreatic cancer remains one of the most deadly afflictions and the fourth leading cause of cancer deaths in the world. Matrix Metalloproteinases (MMPs) are thought to be involved in cancer progression. Matrix metalloproteinase (MMP)-2 is known to play a pivotal role in tumor invasion, metastasis and angiogenesis, and validated to be the anticancer target. Inhibition of MMP-2 activity is able to reduce the cancer cell invasion and suppress tumor growth in vivo. Two novel peptides, M204C4 and M205C4, which could specially inhibit MMP-2 activity, were identified by a phage display library screening. We showed that M204C4 and M205C4 inhibited the activity of MMP-2 in a dose dependent manner in vitro. Two peptides reduced MMP-2 mediated invasion of the pancreatic cancer cell lines PANC-1 and CFPAC-1, but not affected the expression and release of MMP-2. Furthermore, these two peptides could suppress tumor growth in vivo. Our results indicated that two peptides selected by phase display technology may be used as anticancer drugs in the future.
authors.affiliation: Key Laboratory of Human Functional Genomics of Jiangsu Province, Clinical Diabetes Centre of Jiangsu Province, the Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing 210029, Jiangsu, China.
authors.forename: Gao
authors.initials: G
authors.lastname: Lu
authors.forename: Maqing
authors.initials: M
authors.lastname: Zheng
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Zhu
authors.forename: Min
authors.initials: M
authors.lastname: Sha
authors.forename: Yue
authors.initials: Y
authors.lastname: Wu
authors.forename: Xiao
authors.initials: X
authors.lastname: Han
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009368:Neoplasm Transplantation; D009842:Oligopeptides / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D019151:Peptide Library; D010455:Peptides / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011480:Protease Inhibitors / Q000627:therapeutic use*; D014183:Transplantation, Heterologous
chemical_list: D000970:Antineoplastic Agents; C574420:M204C4 peptide; C574421:M205C4 peptide; D061965:Matrix Metalloproteinase Inhibitors; D009842:Oligopeptides; D019151:Peptide Library; D010455:Peptides; D011480:Protease Inhibitors