PDX-1 acts as a potential molecular target for treatment of human pancreatic cancer

Pancreas. 2008 Aug;37(2):210-20. doi: 10.1097/MPA.0b013e31816a4a33.


Objectives: The purpose of this study was to investigate whether pancreatic and duodenal homeobox factor 1 (PDX-1) could serve as a potential molecular target for the treatment of pancreatic cancer.

Methods: Cell proliferation, invasion capacity, and protein levels of cell cycle mediators were determined in human pancreatic cancer cells transfected with mouse PDX-1 (mPDX-1) alone or with mPDX-1 short hairpin RNA (shRNA) and/or human PDX-1 shRNA (huPDX-1 shRNA). Tumor cell growth and apoptosis were also evaluated in vivo in PANC-1 tumor-bearing severe combined immunodeficient mice receiving multiple treatments of intravenous liposomal huPDX-1 shRNA.

Results: mPDX-1 overexpression resulted in the significant increase of cell proliferation and invasion in MIA PaCa2, but not PANC-1 cells. This effect was blocked by knocking down mPDX-1 expression with mPDX-1 shRNA. Silencing of huPDX-1 expression in PANC-1 cells inhibited cell proliferation in vitro and suppressed tumor growth in vivo which was associated with increased tumor cell apoptosis. PDX-1 overexpression resulted in dysregulation of the cell cycle with up-regulation of cyclin D, cyclin E, and Cdk2 and down-regulation of p27.

Conclusions: PDX-1 regulates cell proliferation and invasion in human pancreatic cancer cells. Down-regulation of PDX-1 expression inhibits pancreatic cancer cell growth in vitro and in vivo, implying its use as a potential therapeutic target for the treatment of pancreatic cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Biomarkers, Tumor / antagonists & inhibitors
  • Biomarkers, Tumor / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Homeodomain Proteins / antagonists & inhibitors*
  • Homeodomain Proteins / genetics*
  • Humans
  • Islets of Langerhans / physiopathology
  • Male
  • Mice
  • Mice, SCID
  • Molecular Sequence Data
  • Neoplasm Invasiveness
  • Neoplasm Transplantation
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / physiopathology
  • Pancreatic Neoplasms / therapy*
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Trans-Activators / antagonists & inhibitors*
  • Trans-Activators / genetics*
  • Transfection
  • Transplantation, Heterologous


  • Biomarkers, Tumor
  • Homeodomain Proteins
  • RNA, Small Interfering
  • Trans-Activators
  • pancreatic and duodenal homeobox 1 protein