Growth inhibition of human ovarian cancer cells by blocking STAT3 activation with small interfering RNA

Eur J Obstet Gynecol Reprod Biol. 2010 Jan;148(1):73-80. doi: 10.1016/j.ejogrb.2009.09.018.

Abstract

Objective: Signal transducer and activator of transcription 3 (STAT3) are constitutively activated in a variety of cancers and it is a common feature of ovarian cancer. Thus, STAT3 represents a promising molecular target for tumor therapy. We applied a DNA vector-based STAT3-specific RNA interference approach which specifically blocks over-activated STAT3, to treat human ovarian cancer cells, and evaluated the cellular proliferation ability and investigated the molecular mechanisms in vitro.

Study design: A DNA vector-based RNA interference approach was used to knockdown STAT3 expression in human ovarian cancer cells in vitro.

Results: The STAT3 siRNA down-regulated the expression of cyclin D1, survivin, and VEGF in ovarian cancer cells both at transcription and translation levels. Inhibition of STAT3 and its related genes was accompanied by growth suppression and induction of apoptosis in cancer cells in vitro.

Conclusions: These data indicate that STAT3 signaling is a promising molecular target for ovarian cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyclin D1 / genetics
  • Down-Regulation
  • Female
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Mice
  • Microtubule-Associated Proteins / genetics
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism
  • RNA, Small Interfering / pharmacology*
  • STAT3 Transcription Factor / antagonists & inhibitors*
  • STAT3 Transcription Factor / metabolism*
  • Survivin
  • Transfection
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • RNA, Small Interfering
  • STAT3 Transcription Factor
  • Survivin
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Cyclin D1