LY294002对SGC7901/VCR细胞VCR耐药逆转作用研究  

Drug resistance reversing effects on gastric carcinoma cell line by inhibition of PI3K/PKB signal pathway and its mechanism

作　　者：谢霞[1] 周建云[1] 王雷[1] 郭红[1] 凌贤龙[1] 赵晓晏[1] 

机构地区：[1]第三军医大学新桥医院消化科,重庆400037

出　　处：《重庆医学》2010年第21期2875-2877,F0002,共4页Chongqing medicine

摘　　要：目的观察LY294002对SGC7901/VCR胃癌细胞长春新碱(VCR)耐药的逆转作用,并探讨其可能机制。方法通过MTT法明确LY294002可以逆转SGC7901/VCR对VCR的耐药作用后,采用TUNEL检测细胞的凋亡,高效液相法检测细胞内药物浓度,RT-PCR法和Western blot法分别检测细胞中MDR1、caspase-3和XIAP的基因和蛋白表达水平。结果 LY294002能明显提高VCR的诱导细胞凋亡作用,明显增加细胞内VCR的浓度,并可降低耐药细胞中MDR1、XIAP的基因和升高caspase-3表达水平。结论抑制PI3K/PKB通路可逆转胃癌耐药,其机制可能与降低耐药基因MDR1的表达以及调控凋亡相关基因caspase-3和XIAP的表达有关。Objective To observe whether inhibition of PI3K/AKT signal pathway could reverse drug resistance of gastric carcinoma,and to study its potential mechanism.Methods The growth inhibition effects of VCR alone and VCR in combination with PI3K/PKB inhibitor LY294002 on SGC7901/VCR cells were detected by in vivo and in vitro experiments.The protein and mRNA expression levels of MDR1,caspase-3 and XIAP in SGC7901/VCR cells were determined by Western-blot and reverse transcription PCR.The content of VCR in cells was determined with high performance liquid chromatography（HPLC）.Besides,the apoptosis was detected by TUNEL.Results LY294002 enhanced the sensitivities of SGC7901/VCR cells to VCR significantly,and promoted the apoptosis rate induced by VCR prominently.The protein and gene expression levels of MDR1 and XIAP were inhibited,while the expression of caspase-3 was improved significantly.When VCR coupled with the LY294002,the VCR accumulation in cells increased significantly than used only.Conclusion Inhibition of PI3K/PKB signal pathway by LY294002 can reverse the drug resistance of gastric carcinoma cell line.Reduction of MDR1 expression levels,and regulation of apoptosis related genes,such as caspase-3 and XIAP expression levels play key roles in this progress.

关 键 词：LY294002 SGC7901/VCR细胞 凋亡 MDR1 

分 类 号：R735.2[医药卫生—肿瘤] R730.53[医药卫生—临床医学]