STAT3-decoy oligodeoxynucleotide inhibits the growth of human lung cancer via down-regulating its target genes

Oncol Rep. 2007 Jun;17(6):1377-82.

Abstract

Double-stranded decoy oligodeoxynucleotide (ODN) is a promising approach for inhibiting gene transcription. Signal transducer and activator of transcription (STAT) 3, a potent transcription factor, is usually constitutively activated in a variety of malignancies, and considered as an attractive drug target. In this study, it was noted that STAT3 was overactivated in human lung cancer cells, and STAT3-decoy ODN, which was high-efficiently transfected into nucleus of cancer cells, significantly inhibited the proliferation of PG cells by inducing apoptosis or cell cycle arrest. The transcription levels of mcl-1, cyclin D1, bcl-xl and survivin were significantly decreased by 64.4, 56.1, 72.8% (P<0.01) and 31.8% (P<0.05), respectively; and the synthesis levels of bcl-xl and cyclin D1 in PG cells showed 64.5% (P<0.01) and 28.6% (P<0.05) decrease, respectively. Our study demonstrated that decoy-ODN targeting at activated STAT3 may potentially be used as an anti-lung cancer therapeutic approach.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyclin D1 / antagonists & inhibitors
  • Cyclin D1 / genetics
  • Down-Regulation
  • Gene Expression / drug effects
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Lung Neoplasms / genetics*
  • Microtubule-Associated Proteins / antagonists & inhibitors
  • Microtubule-Associated Proteins / genetics
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics
  • Oligodeoxyribonucleotides / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • STAT3 Transcription Factor / antagonists & inhibitors*
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism
  • Survivin
  • Transfection
  • bcl-X Protein / antagonists & inhibitors
  • bcl-X Protein / genetics

Substances

  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neoplasm Proteins
  • Oligodeoxyribonucleotides
  • Proto-Oncogene Proteins c-bcl-2
  • STAT3 Transcription Factor
  • Survivin
  • bcl-X Protein
  • Cyclin D1