Triplex-forming oligodeoxynucleotides targeting survivin inhibit proliferation and induce apoptosis of human lung carcinoma cells

Cancer Gene Ther. 2003 May;10(5):403-10. doi: 10.1038/sj.cgt.7700581.


Survivin is expressed in most cancers but is undetectable in differentiated adult cells, and plays an important role both in the suppression of apoptosis and mitotic spindle checkpoint; thus it has attracted great interest as a potential drug target. In this study, we investigated the antigene and antiproliferative effects of triplex-forming oligodeoxynucleotides (TFO) targeting survivin in human lung carcinoma A549 cells. Survivin-specific TFOs form stable triplexes under physiological conditions as tested by electrophoretic mobility shift assays. Treatment of A549 cells with survivin-specific but not control TFOs at a concentration of 400 nM in the presence of uptake-enhancing liposome significantly reduced survivin protein level, inhibited cell proliferation, and induced cell apoptosis as demonstrated by immunoblot, cell number counting, and Annexin V-staining. Moreover, we found that the triplex-forming potential of TFOs measured in vitro does not necessarily correlate with the ability of TFOs to affect expression of a targeted gene in vivo. Our results indicate that targeting survivin is a promising alternative strategy for the development of novel anticancer therapeutics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Annexin A5 / metabolism
  • Apoptosis / drug effects*
  • Cell Count
  • Cell Division / drug effects
  • DNA Primers / chemistry
  • Electrophoretic Mobility Shift Assay
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Liposomes
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Microtubule-Associated Proteins / genetics*
  • Microtubule-Associated Proteins / metabolism
  • Neoplasm Proteins
  • Nucleic Acid Conformation
  • Oligodeoxyribonucleotides / pharmacology*
  • Survivin
  • Tumor Cells, Cultured


  • Annexin A5
  • BIRC5 protein, human
  • DNA Primers
  • Inhibitor of Apoptosis Proteins
  • Liposomes
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Oligodeoxyribonucleotides
  • Survivin