靶向FAK基因RNAi联合吉西他滨抗非小细胞肺癌的作用
Effect of shRNA targeting FAK combined with Gemcitabine on non-small cell lung cancer
作者：杨玲麟;汪碧琼;陈岚岚;罗惠群;任培蓉;王利群;吴敬波;
Author：
收稿日期： 年卷（期）页码：2012,27(05):-513-517
期刊名称：华西药学杂志
Journal Name：WEST CHINA JOURNAL OF PHARMACEUTICAL SCIENCES
关键字：局部粘着斑激酶;短发卡RNA;吉西他滨;凋亡;靶向;肺癌
Key words：
基金项目：四川省教育厅川教函[2010]597号资助(项目编号:10ZB028)
中文摘要
目的探讨通过RNAi下调非小细胞肺癌局部粘着斑激酶(FAK)的活性后对吉西他滨药理的影响。方法靶向FAK的shRNA重组质粒转染并下调细胞FAK蛋白表达,用Western Blot检测转染细胞中FAK的下调;利用MTT检测吉西他滨在不同浓度下对转染细胞增殖的影响;用流式细胞术、PI荧光染色检测吉西他滨作用下转染细胞的凋亡;Caspase与Akt活性分别用Apo-ONETM均质Caspase-3/7检测系统、Western blot检测。结果在吉西他滨不参与的情况下,FAK RNAi不能影响细胞的增殖和凋亡,但FAK RNAi明显增加了吉西他滨对肿瘤细胞的灵敏度,Akt活性的下调与这一现象有关。结论靶向FAK的shRNA重组质粒下调细胞FAK蛋白表达能够增加吉西他滨对非小细胞肺癌的细胞毒性。
参考文献
[1]Parsons JT.Focal adhesion kinase:The first ten years[J].J CellSci,2003,116:1409-1416.
[2]Khuri FR,Herbst RS,Fossella FV.Emerging therapies in nonsmall-cell lung cancer[J].Ann Oncol,2001,12:739-744.
[3]Soria JC,Jiang SJ,Khuri FR,et al.Overexpression of cyclin B1 inearly-stage non-small cell lung cancer and its clinical implica-tion[J].Cancer Res,2000,60:4000-4004.
[4]尤长宣,罗荣城.治疗非小细胞肺癌的新药吉西他滨[J].国外医学肿瘤学分册,2000,27(5):309-311.
[5]WG Cance,JEH,MV,et al.Immunohistochemical analyses of fo-cal adhesion kinase expression in benign and malignant humanbreast and colon tissues:correlation with preinvasive and invasivephenotypes[J].Clin Cancer Res,2000,6:2417-2423.
[6]NM Han,RF,SA Curley,et al.Overexpression of focal adhesionkinase(p125FAK)in human colorectal carcinoma liver metasta-ses:Independence from c-src or c-yes activation[J].AnnSurg Oncol,1997,4:264-268.
[7]LV Owens,LX,RJ Craven,et al.Overexpression of the focal ad-hesion kinase(p125FAK)in invasive human tumors[J].CancerRes,1995,55:2752-2755.
[8]Maroesja J,van Nimwegen,B vd W.Focal adhesion kinase:Apotential target in cancer therapy[J].Biochem Pharmacol,2007,73:597–609.
[9]B Van de Water,F H,M Huigsloot,et al.Suppression of chemi-cally induced apoptosis but not necrosis of renal proximal tubularepithelial(LLC-PK1)cells by focal adhesion kinase(FAK)[J].J Biol Chem,2001,276:36183-36193.
[10]Tuschl T.Expanding small RNA interference[J].Nat Biotechnol,2002,5:446-448.
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