OSW-1与线粒体DNA缺失对肝癌细胞PI3K信号通路的影响  

Effect of OSW-1 and deletion of mitochondrial DNA on PI3K signaling pathway in hepatoma carcinoma cell

作　　者：张晓威 李娜 金吉春[2] 金星林[2] 

机构地区：[1]广东省惠州市惠东县人民医院,广东惠州516300 [2]延边大学附属医院,吉林延吉133000

出　　处：《吉林医学》2016年第8期1849-1852,共4页Jilin Medical Journal

摘　　要：目的:探讨OSW-1与线粒体DNA缺失对肝癌细胞PI3K信号通路的影响。方法:以SK-Hep-1细胞为对照组,建立线粒体DNA缺失的ρ0-SK-Hep-1细胞模型(试验组2),使用荧光实时定量PCR芯片比较两组细胞PI3K信号通路的表达差异。OSW-1干预SK-Hep-1(试验组1)及ρ0-SK-Hep-1(试验组3)细胞24 h后,使用荧光实时定量PCR芯片比较两组细胞PI3K信号通路的表达差异。结果:SK-Hep-1细胞线粒体DNA缺失后细胞信号传导通路中基因:CASP9、CD14、FOXO1、GJA1、GRB2、HSPB1、IGF1、MAPK3、PDPK1、PRKCA、RPS6KA1、TLR4、TSC2表达上调;APC、CTNNB1表达下调。OSW-1作用于SK-Hep-1细胞后细胞信号传导通路中基因:FOS、GRB2、HSPB1、IRAK1、PDPK1、PRKCA、PRKCB、TLR4、TOLLIP、TSC2表达上调;APC、IGF1、IRS1、PDGFRA、PTPN11、SHC1表达下调。OSW-作用ρ0-SK-Hep-1细胞后细胞信号传导通路中基因:AKT1、CDC42、CDKN1B、FASLB、IRAK1、IRS1、PDGFRA、PDK2、PIK3R2、PRKCB、SHC1、TIRAP、TOLLIP等表达上调。BAD、EIF2AK2、FOXO1、IGF1、PABPC1、PAK1、PDK1、PDPK1、PIK3CG、RAC1、RASA1、RHOA、SOS1、TLR4、WASL等表达下调。结论:OSW-1和线粒体DNA缺失均能影响SK-Hep-1细胞PI3K信号传导通路基因的表达。OSW-1靶向作用于SK-Hep-1细胞的线粒体,抑制其功能。OSW-1靶向抑制肝癌细胞IGF-1-PI3K-AKT信号传导通路;Grb2-p85-AKT信号传导通路;IRS1-PI3K-AKT-GLUT-4信号传导通路;PI3K-AKT-TSC1/TSC2-m TOR信号传导通路;TLR4-PI3K-AKT细胞信号传导通路,从而抑制肝癌细胞生长、增殖、能量代谢。Objective To study the effect of OSW-1 and deletion of mitochondrial DNA on PI3K signaling pathway in hepa-toma carcinoma cell.Method Establish the mitochondrial DNA deletion model,ρ0 -SK -Hep -1（e.g.2）,which was maked of the SK -Hep -1 cell（c.g.）as the control group.Compare the difference of expression between SK -Hep -1 andρ0 -SK -Hep-1 cell on PI3K signaling pathway by a quantitative real -time PCR Assay.SK -Hep -1 （e.g.1）and ρ0 -SK -Hep -1 （e.g.3）cell are intervened by OSW-1 24 h,and compare the two groups′different expression.Results The up -regulated ex-pression of experimental group 1 compares with control group：CASP9、CD14、FOXO1、GJA1、GRB2、HSPB1、IGF1、MAPK3、PD-PK1、PRKCA、RPS6KA1、TLR4、TSC2.The down -regulated expression of experimental group 1 compares with control group：APC、CTNNB1.The up -regulated expression of experimental group 2 compares with control group：FOS、GRB2、HSPB1 、I-RAK1、PDPK1、PRKCA、PRKCB、TLR4 、TOLLIP、TSC2.The down -regulated expression of experimental group 2 compares with control group：APC、IGF1、IRS1、PDGFRA、PTPN11、SHC1.The up -regulated expression of experimental group 3 compares with control group：AKT1、CDC42、CDKN1B、FASLB、IRAK1、IRS1、PDGFRA、PDK2、PIK3R2、PRKCB、SHC1、TIRAP、TOLLIP.The down -regulated expression of experimental group 3 compares with control group：BAD、EIF2AK2、FOXO1、IGF1、PABPC1、PAK1、PDK1、PDPK1、PIK3CG、RAC1、RASA1、RHOA、SOS1、TLR4、WASL.Conclusion OSW -1 and deletion of mi-tochondrial DNA could effect the expression of PI3K signaling pathway in SK -Hep -1 cell.The targeting effects of OSW-1 on the mitochondria of SK -Hep -1 was proved.OSW-1 inhibited IGF -1 -PI3K -AKT,Grb2 -p85 -AKT,IRS1 -PI3K -AKT-GLUT -4,PI3K -AKT -TSC1 /TSC2 -mTOR and TLR4 -PI3K -AKT signaling pathway to inhibit hepatoma carcinoma cell′s growth,multiplication,energy metabolism.

关 键 词：肝癌 OSW-1 PI3K信号通路 实时定量PCR芯片 

分 类 号：R735.7[医药卫生—肿瘤]