siRNA directed against c-Src enhances pancreatic adenocarcinoma cell gemcitabine chemosensitivity

被引：64

作者：

Duxbury, MS ^{[1
]}

Ito, H ^{[1
]}

Zinner, MJ ^{[1
]}

Ashley, SW ^{[1
]}

Whang, EE ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA

来源：

JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS | 2004年 / 198卷 / 06期

关键词：

D O I：

10.1016/j.jamcollsurg.2004.01.037

中图分类号：

R61 [外科手术学];

学科分类号：

摘要：

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. (C) 2004 by the American College of Surgeons.

引用

页码：953 / 959

页数：7