RNA interference targeting focal adhesion kinase enhances pancreatic adenocarcinoma gemcitabine chemosensitivity

Mark S. Duxbury, Hiromichi Ito, Eric Benoit, Michael J. Zinner, Stanley W. Ashley, Edward E. Whang

Research output: Contribution to journalArticle

Abstract

Focal adhesion kinase (FAK) is an important regulator of cellular signaling, migration, apoptosis, and cell cycle progression. We tested the hypothesis that FAK is a determinant of gemcitabine chemoresistance in pancreatic adenocarcinoma cells and examined the effect of inhibiting FAK expression on gemcitabine-induced cytotoxicity in vitro and in vivo. FAK expression was quantified by Western and Northern blots. Expression of FAK was suppressed using small interfering RNA (siRNA). Gemcitabine-induced cytotoxicity was quantified and apoptosis was characterized. Akt activity was determined by in vitro kinase assay. We assessed the therapeutic applicability of FAK siRNA in a nude mouse orthotopic xenograft model. While not affecting cellular proliferation or apoptosis in the absence of gemcitabine, FAK siRNA potentiated gemcitabine-induced cytotoxicity in vitro and in vivo. FAK siRNA treatment suppressed Akt activity, which may contribute to its chemosensitizing effect.

Original languageEnglish (US)
Pages (from-to)786-792
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume311
Issue number3
DOIs
StatePublished - Nov 21 2003

Keywords

  • Adenocarcinoma
  • Cancer
  • FAK
  • Focal adhesion kinase
  • Gemcitabine
  • Interference
  • Pancreatic
  • RNA
  • siRNA

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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