siRNA directed against c-Src enhances pancreatic adenocarcinoma cell gemcitabine chemosensitivity - 24/08/11
, Hiromichi Ito, MD , Michael J Zinner, MD : FACS, Stanley W Ashley, MD : FACS, Edward E Whang, MD , ⁎ : FACS Department of Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA Abstract |
Background |
The c-Src tyrosine kinase is a determinant of malignant cellular behavior in a variety of human cancers. We sought to determine the effect of suppressing c-Src expression on pancreatic adenocarcinoma chemosensitivity to gemcitabine.
Study design |
PANC1, MIAPaCa2, BxPC3, and Capan2 pancreatic adenocarcinoma cell lines were studied. Expression of c-Src was determined by Western blot analysis. c-Src kinase activity was determined by in vitro kinase assay. RNA interference was used to suppress c-Src expression. Gemcitabine-induced cytotoxicity was determined by tetrazolium reduction assay and caspase profiling was performed. The effect of Src-specific siRNA on Akt activity was quantified.
Results |
Src expression and kinase activity in cell lines were directly correlated with gemcitabine chemoresistance. c-Src-specific siRNA suppressed c-Src expression and kinase activity. c-Src-specific siRNA increased gemcitabine-induced, caspase-mediated apoptosis. Akt activity was decreased by suppression of c-Src expression.
Conclusions |
c-Src is a determinant of pancreatic adenocarcinoma chemoresistance and represents a potential target for therapeutic intervention.
Le texte complet de cet article est disponible en PDF.Abbreviations : GSK-3, IC50, MTT, siRNA
Plan
Vol 198 - N° 6
P. 953-959 - juin 2004 Retour au numéro
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