title: An antimicrobial peptide containing NGR motif has potent antitumor activity against CD13+ and CD13- tumor cells.
abstract: Antimicrobial peptides (AMPs) with Asn-Gly-Arg (NGR) motif have potent cytotoxicity, preferably against tumor cells due to their binding to CD13 on tumor cells. However, the importance of αvβ3 expression for antitumor activity of AMPs containing NGR has not been clarified. This study was aimed at designing a new AMP containing NGR and testing their biological activity against different types of tumor cells with varying CD13 and αvβ3 expression. We first synthesized the new AMP containing NGR motif (CK21), which effectively entered into CD13+ HT-1080, but less into CD13- αvβ3+ MDA-MB-435 and further less into stable αvβ3-silencing MDA-MB-435 cells. Furthermore, CK21 displayed dose-dependent antiproliferation against these tumor cells and induced cell cycling arrest at G2/M phases and apoptosis of these tumor cells. In addition, CK21 inhibited the invasion of these tumor cells in vitro and inhibited the growth of implanted tumor cells in vivo. Particularly, the antitumor effect of CK21 in CD13+ HT-1080 was stronger than that of CD13- αvβ3+ MDA-MB-435 and much stronger than that of stable αvβ3-silencing MDA-MB-435. Our data indicated that the new AMPs containing NGR had potent antitumor activity against CD13+ or αvβ3+ tumor cells, preferably against CD13+ tumor cells, possibly through binding to CD13 or αvβ3 on tumor cells.
authors.affiliation: Department of Traditional Chinese Medicine, The First Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, People's Republic of China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, 710068, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Hou
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Medical School of Xi'an Jiaotong University, 227 Yanta West Road, Xi'an, Shaanxi, 710061, People's Republic of China.
authors.forename: Lu
authors.initials: L
authors.lastname: Feng
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Medical School of Xi'an Jiaotong University, 227 Yanta West Road, Xi'an, Shaanxi, 710061, People's Republic of China.
authors.forename: Shangke
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Medical School of Xi'an Jiaotong University, 227 Yanta West Road, Xi'an, Shaanxi, 710061, People's Republic of China.
authors.forename: Minna
authors.initials: M
authors.lastname: Luo
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Medical School of Xi'an Jiaotong University, 227 Yanta West Road, Xi'an, Shaanxi, 710061, People's Republic of China.
authors.forename: Shan
authors.initials: S
authors.lastname: Shao
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Medical School of Xi'an Jiaotong University, 227 Yanta West Road, Xi'an, Shaanxi, 710061, People's Republic of China.
authors.forename: Xiaojin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Forensic Medicine, Medical School of Xi'an Jiaotong University, 76 Yanta West Road, Xi'an, Shaanxi, 710061, People's Republic of China. gushanzhi@mail.xjtu.edu.cn.
authors.forename: Shanzhi
authors.initials: S
authors.lastname: Gu
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Medical School of Xi'an Jiaotong University, 227 Yanta West Road, Xi'an, Shaanxi, 710061, People's Republic of China. zhaoxinhanprof@163.com.
authors.forename: Xinhan
authors.initials: X
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D018826:CD13 Antigens / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D009842:Oligopeptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000900:Anti-Bacterial Agents; C526428:NGR peptide; D009842:Oligopeptides; D010446:Peptide Fragments; D018826:CD13 Antigens
keywords: Antimicrobial peptides; Antitumor activity; CD13; NGR motif; αvβ3