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.[1]References
- Polo-like kinase1, a new target for antisense tumor therapy. Elez, R., Piiper, A., Giannini, C.D., Brendel, M., Zeuzem, S. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
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