Inhibition of Human Osteosarcoma Cell Migration and Invasion by a Gene Silencer, Pyrrole–Imidazole Polyamide, Targeted at the Human MMP9 NF-κB Binding Site Inhibition of Human Osteosarcoma Cell Migration and Invasion by a Gene Silencer, Pyrrole–Imidazole Polyamide, Targeted at the Human MMP9 NF-κB Binding Site

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Author(s)

    • Kojima Toshio Kojima Toshio
    • Department of Orthopedic Surgery, Nihon University School of Medicine|Division of Cancer Genetics, Department of Advanced Medical Science, Nihon University School of Medicine
    • Wang Xiaofei Soma Masayoshi
    • Innovative Therapy Research Group, Nihon University Research Institute of Medical Science, Nihon University School of Medicine|Division of General Medicine, Department of Medicine, Nihon University School of Medicine
    • Nagase Hiroki
    • Division of Cancer Genetics, Department of Advanced Medical Science, Nihon University School of Medicine|Life Science, Advanced Research Institute for the Sciences and Humanities, Nihon University|Innovative Therapy Research Group, Nihon University Research Institute of Medical Science, Nihon University School of Medicine|Division of Cancer Genetics, Chiba Cancer Center Research Institute
    • Wang Xiaofei
    • Division of Cancer Genetics, Department of Advanced Medical Science, Nihon University School of Medicine|Life Science, Advanced Research Institute for the Sciences and Humanities, Nihon University
    • Fujiwara Kyoko
    • Innovative Therapy Research Group, Nihon University Research Institute of Medical Science, Nihon University School of Medicine|Division of General Medicine, Department of Medicine, Nihon University School of Medicine
    • Osaka Shunzo
    • Department of Orthopedic Surgery, Nihon University School of Medicine
    • Osaka Eiji
    • Department of Orthopedic Surgery, Nihon University School of Medicine
    • Ueno Takahiro
    • Innovative Therapy Research Group, Nihon University Research Institute of Medical Science, Nihon University School of Medicine|Division of Nephrology, Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine
    • Fukuda Noboru
    • Innovative Therapy Research Group, Nihon University Research Institute of Medical Science, Nihon University School of Medicine|Division of Nephrology, Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine

Abstract

Osteosarcoma is one of the most prevalent bone tumors, occurring mostly in adolescence. However, no noticeable progress has been achieved in developing new therapeutic agents for this disease. Matrix metalloproteinase 9 (MMP9), a type IV collagenase, is a known anticancer target and is overexpressed in osteosarcomas. MMPs can degrade components of the extracellular matrix and are known to be involved in tumor invasion and metastasis. In the present study, we designed and synthesized a pyrrole–imidazole polyamide (HN.49), a gene-silencing agent that specifically targets the nuclear factor-kappa B (NF-κB) binding site of the human MMP9 promoter. We then examined the effect of HN.49 on the enzyme activity of MMP9 and the migration activity of osteosarcoma cells <i>in vitro</i>. It was clearly shown that HN.49 polyamide reduced the expression level of MMP9 mRNA and the enzymatic activity of MMP-9 in SaOS-2 cells. Moreover, HN.49 polyamide inhibited migration and invasion by SaOS-2 cells in <i>in vitro</i> wound-closure and matrigel-invasion assays. These results indicate that HN.49 may be a potential therapeutic agent for inhibiting the invasion and metastasis of osteosarcoma.

Journal

  • Biological and Pharmaceutical Bulletin

    Biological and Pharmaceutical Bulletin 37(9), 1460-1465, 2014

    The Pharmaceutical Society of Japan

Codes

  • NII Article ID (NAID)
    130004684785
  • NII NACSIS-CAT ID (NCID)
    AA10885497
  • Text Lang
    ENG
  • ISSN
    0918-6158
  • NDL Article ID
    025736808
  • NDL Call No.
    Z53-V41
  • Data Source
    NDL  J-STAGE 
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