Format

Send to

Choose Destination
See comment in PubMed Commons below
Cancer Lett. 2010 May 1;291(1):90-8. doi: 10.1016/j.canlet.2009.10.001. Epub 2009 Oct 31.

Downregulation of nuclear factor-kappaB p65 subunit by small interfering RNA synergizes with gemcitabine to inhibit the growth of pancreatic cancer.

Author information

1
The Hepatosplenic Surgery Center, Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, China.

Abstract

The clinical benefit of gemcitabine for pancreatic cancer is low due to chemoresistance. Nuclear factor (NF)-kappaB, constitutively activated in pancreatic cancer, is a therapeutic target as it upregulates expression of genes controlling proliferation, apoptosis and angiogenesis. This study aimed to investigate whether downregulation of the p65 subunit of NF-kappaB by siRNA could enhance the efficacy of gemcitabine to treat pancreatic cancer. p65 siRNA synergized with gemcitabine to inhibit the proliferation and induce the apoptosis of pancreatic cancer cells in vitro and in vivo, and suppress the growth and angiogenesis of pancreatic tumors in nude mice. The mechanisms involved inhibition of NF-kappaB activity and consequent inhibition of Bcl-2, cyclin D1 and VEGF, and activation of caspase-3. The results suggest that downregulation of NF-kappaB p65 potentiates the efficacy of gemcitabine in combating pancreatic cancer.

PMID:
19880242
DOI:
10.1016/j.canlet.2009.10.001
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center