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

The Polo-like kinase 1 (Plk1) is a highly conserved mitotic serine/threonin e kinase which is commonly overexpressed in cancer cell lines. Plk1 positiv ely regulates mitotic progression by activating the CDC25C-CDK1 amplificati on loop and by regulating late mitotic events, primarily the ubiquitin-depe ndent proteolysis. In the present study, an antisense strategy against Plk1 mRNA was developed to specifically inhibit cell proliferation of cancer ce lls in cell culture and in the nude-mouse tumor model. Among 41 phosphoroth ioate antisense oligodeoxynucleotides tested, the 20-mer JWG2000 strongly i nhibited 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 cel ls and human amnion fibroblasts. (C) 2000 Academic Press.