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

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

Author information

1
Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA.

Abstract

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.

PMID:
18665085
DOI:
10.1097/MPA.0b013e31816a4a33
[Indexed for MEDLINE]
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