Polo-like kinase1, a new target for antisense tumor therapy

Biochem Biophys Res Commun. 2000 Mar 16;269(2):352-6. doi: 10.1006/bbrc.2000.2291.

Abstract

The Polo-like kinase 1 (Plk1) is a highly conserved mitotic serine/threonine kinase which is commonly overexpressed in cancer cell lines. Plk1 positively regulates mitotic progression by activating the CDC25C-CDK1 amplification loop and by regulating late mitotic events, primarily the ubiquitin-dependent proteolysis. In the present study, an antisense strategy against Plk1 mRNA was developed to specifically inhibit cell proliferation of cancer cells in cell culture and in the nude-mouse tumor model. Among 41 phosphorothioate antisense oligodeoxynucleotides tested, the 20-mer JWG2000 strongly inhibited expression of Plk1 in cultured A549 cells, leading to loss of cell viability, and exhibited anti-tumor activity in nude mice A549 xenograft. JWG2000 did not inhibit growth and viability of primary human mesangial cells and human amnion fibroblasts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Cell Cycle Proteins
  • Cell Division / drug effects
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Mice
  • Mice, Nude
  • Oligodeoxyribonucleotides / pharmacology*
  • Oligonucleotides, Antisense / pharmacology*
  • Protein Kinase Inhibitors*
  • Protein Kinases*
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins
  • Thionucleotides / pharmacology
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Cell Cycle Proteins
  • Enzyme Inhibitors
  • JWG 2000
  • Oligodeoxyribonucleotides
  • Oligonucleotides, Antisense
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins
  • Thionucleotides
  • Protein Kinases
  • Protein-Serine-Threonine Kinases
  • polo-like kinase 1