RNA interference targeting focal adhesion kinase enhances pancreatic adenocarcinoma gemcitabine chemosensitivity
RNA interference targeting focal adhesion kinase enhances pancreatic adenocarcinoma gemcitabine chemosensitivity
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DOI：
10.1016/j.bbrc.2003.10.060
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发表时间：
2003-11-21
影响因子：
3.1
通讯作者：
Whang, EE
中科院分区：
文献类型：
--
作者：
Duxbury, MS;Ito, H;Whang, EE
粘着斑激酶（FAK）是细胞信号传导、迁移、凋亡和细胞周期进程的重要调节因子。我们检验了FAK是胰腺癌细胞吉西他滨化疗耐药性决定因素的假设，并研究了抑制FAK表达对吉西他滨诱导的体外和体内细胞毒性的影响。通过蛋白质印迹和北方印迹定量FAK表达。使用小干扰RNA（siRNA）抑制FAK的表达。定量吉西他滨诱导的细胞毒性并表征细胞凋亡。Akt活性通过体外激酶测定法测定。我们评估了FAK siRNA在裸鼠原位异种移植模型中的治疗适用性。虽然在没有吉西他滨的情况下不影响细胞增殖或凋亡，但FAK siRNA在体外和体内增强了吉西他滨诱导的细胞毒性。FAK siRNA处理抑制Akt活性，这可能有助于其化学增敏作用。(C)2003年爱思唯尔公司All rights reserved.
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. (C) 2003 Elsevier Inc. All rights reserved.