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 language | English (US) |
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Pages (from-to) | 786-792 |
Number of pages | 7 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 311 |
Issue number | 3 |
DOIs | |
State | Published - 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