Polo-like kinase1, a new target for antisense tumor therapy.
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.
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Department of Medicine II, Institut für Mikrobiologie, J. W. Goethe-Universität, Theodor-Stern-Kai 7, Haus 75, Frankfurt, 60590, Germany.
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Giannini
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Brendel
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Zeuzem
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D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D013873:Thionucleotides / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D000097869:Polo-Like Kinase 1
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D013873:Thionucleotides; D000097869:Polo-Like Kinase 1; C406329:JWG 2000