Antisense Oligonucleotides Targeting Y-Box Binding Protein-1 Inhibit Tumor Angiogenesis by Downregulating Bcl-xL-VEGFR2/-Tie Axes.

ABSTRACT: Y-box binding protein-1 (YB-1), involved in cancer progression and chemoradiation resistance, is overexpressed in not only cancer cells but also tumor blood vessels. In this study, we investigated the potential value of amido-bridged nucleic acid (AmNA)-modified antisense oligonucleotides (ASOs) targeting YB-1 (YB-1 ASO^A) as an antiangiogenic cancer therapy. YB-1 ASO^A was superior to natural DNA-based ASO or locked nucleic acid (LNA)-modified YB-1 ASO in both knockdown efficiency and safety, the latter assessed by liver function. YB-1 ASO^A administered i.v. significantly inhibited YB-1 expression in CD31-positive angiogenic endothelial cells, but not in cancer cells, in the tumors. With regard to the mechanism of its antiangiogenic effects, YB-1 ASO^A</

SUBMITTER: Setoguchi K 

PROVIDER: S-EPMC5633255 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature