Optimal sequence of antisense DNA to silence YB-1 in lung cancer by use of a novel polysaccharide drug delivery system

Int J Oncol. 2016 Jun;48(6):2472-8. doi: 10.3892/ijo.2016.3451. Epub 2016 Mar 23.

Abstract

Silencing Y-box binding protein 1 (YB-1) can be an excellent target for cancer therapy and many lung cancer cells express the polysaccharide-recognition receptor Dectin-1. We designed a Dectin-1 targeting vehicle delivering YB-1-antisense DNA. First, we selected five optimal antisense DNA sequences to silence YB-1 from among 153 candidates. We chose the sequence closest to the start codon (AS014), and attached dA40 to the 3' end; dA40 promotes complex formation with a β-(1➝3)-d-glucan called schizophyllan (SPG). The resultant complexes were applied to 12 human-oriented lung cancer cell lines, and cell viability was examined. The cell lines exhibited decreased viability and showed strong affinity to bind SPG, suggesting the AS014/SPG complex entered the cells via the Dectin-1 mediated pathway.

MeSH terms

  • Base Sequence
  • Cell Line
  • Cell Survival / drug effects
  • DNA, Antisense / chemistry
  • DNA, Antisense / genetics
  • DNA, Antisense / pharmacology*
  • Drug Delivery Systems
  • Gene Silencing
  • Humans
  • Lectins, C-Type / chemistry*
  • Lung Neoplasms / genetics*
  • Sizofiran / chemistry*
  • Y-Box-Binding Protein 1 / antagonists & inhibitors
  • Y-Box-Binding Protein 1 / genetics*

Substances

  • DNA, Antisense
  • Lectins, C-Type
  • Y-Box-Binding Protein 1
  • YBX1 protein, human
  • dectin 1
  • Sizofiran