LY294002联合吉西他滨对胰腺癌PANC-1细胞p-Akt和MRP表达的影响  

LY294002 combined with gemcitabine inhibits p-Akt and MRP expression in human pancreatic carcinoma PANC-1 cells

作　　者：柯晓煜[1] 王渝[2] 谢祚启[1] 刘志清[1] 赵秋[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院消化内科,湖北省武汉市430030 [2]华中科技大学同济医学院附属同济医院病理科,湖北省武汉市430030

出　　处：《世界华人消化杂志》2011年第36期3678-3681,共4页World Chinese Journal of Digestology

摘　　要：目的:研究LY294002联合吉西他滨对体外培养的人胰腺癌PANC-1细胞内p-Akt和MRP表达的作用.方法:半定量RT-PCR和Western blot检测不同浓度的LY294002联合吉西他滨用药后PANC-1细胞内MRP mRNA以及p-Akt和MRP蛋白表达水平的变化.结果:LY294002联合吉西他滨能显著抑制PANC-1细胞内MRP mRNA的表达(1.47±0.03,1.31±0.05,1.02±0.04,0.76±0.06,0.37±0.02,P<0.05),亦显著抑制p-Akt和MRP蛋白的表达,并且这种抑制作用与药物浓度显著相关(p-Akt:0.80±0.02,0.63±0.01,0.52±0.01,0.41±0.02,0.35±0.02,P<0.05;MRP:0.93±0.05,0.87±0.03,0.81±0.03,0.71±0.02,0.40±0.03,P<0.05),在其浓度最大组抑制效应达到最大.结论:LY294002可能通过抑制PI3K/Akt信号途径抑制MRP mRNA和蛋白的表达,逆转肿瘤的耐药.AIM：To investigate the effect of LY294002 （a PI3K inhibitor） combined with gemcitabine on p-Akt and multidrug resistance-associated protein （MRP） expression in human pancreatic carcinoma PANC-1 cells.METHODS：After PANC-1 cells were treated with different concentrations of LY294002 and gemcitabine,the expression of MRP mRNA and p-Akt and MRP proteins was detected by semi-quantitative RT-PCR and Western blot,respectively.RESULTS：Compared to untreated control cells,treatment with LY294002 combined with gemcitabine significantly decreased the expression of MRP mRNA （1.47±0.03,1.31±0.05,1.02±0.04,0.76±0.06,0.37±0.02,P0.05） and p-Akt and MRP proteins （p-Akt：0.80±0.02,0.63±0.01,0.52±0.01,0.41±0.02,0.35±0.02,P0.05;MRP：0.93±0.05,0.87±0.03,0.81±0.03,0.71±0.02,0.40±0.03,both P0.05） in a concentration-dependent manner.CONCLUSION：LY294002 could effectively strengthen the sensitivity of human pancreatic carcinoma PANC-1 cells to gemcitabine.LY294002 may down-regulate MRP transcription by inhibiting p-Akt expression and therefore reverse resistance of PANC-1 cells to gemcitabine.

关 键 词：LY294002 吉西他滨 PANC-1细胞 P-AKT MRP 

分 类 号：R735.9[医药卫生—肿瘤]