姜黄素通过β-Catenin/BCL9信号通路介导的细胞自噬调节肝癌细胞的恶性生物学行为  

Curcumin Regulates the Malignant Biological Behaviors of Hepatocellular Carcinoma Cells Through Autophagy Mediated byβ-Catenin/BCL9 Signaling Pathway

作　　者：鲁猛[1] 王刚[1] 贾洪艳 李洋 张磊[1] 张秋学[1] 李学峰[1] 王娜[2] LU Meng;WANG Gang;JIA Hongyan;LI Yang;ZHANG Lei;ZHANG Qiuxue;LI Xuefeng;WANG Na(Cangzhou Central Hospital,Cangzhou Hebei 061000,China;Hebei Medical University,Shijiazhuang Hebei 050011,China)

机构地区：[1]沧州市中心医院,河北沧州061000 [2]河北医科大学,河北石家庄050011

出　　处：《中医药导报》2023年第9期12-17,共6页Guiding Journal of Traditional Chinese Medicine and Pharmacy

基　　金：河北省2022年度医学科学研究课题项目(20220389)。

摘　　要：目的:探讨姜黄素(Cur)调控β-Catenin/BCL9通路对肝癌细胞HepG2自噬反应及生物学行为的影响。方法:将HepG2细胞分为对照组(Control组)、Cur组(20.0μmol/L)、Cur+自噬抑制剂组[Cur(20.0μmol/L)+3-MA(5.0 mmol/L)]、Cur+质粒对照组[Cur(20.0μmol/L)+VEC]、Cur+Bcl9过表达组[Cur(20.0μmol/L)+OE-BCL9]、Cur+shRNA慢病毒载体阴性对照组[Cur(20.0μmol/L)+Sh-NC]、Cur+shRNA BCL9慢病毒载体组[Cur(20.0μmol/L)+Sh-BCL9],分别检测HepG2细胞凋亡、迁移与侵袭,观察自噬体的形成与自噬体水平,Western blotting检测自噬(LC3Ⅱ/Ⅰ、Beclin1)、上皮间质转化(Vimentin、E-cadherin)、β-Catenin/BCL9通路(BCL9、β-Catenin)相关蛋白相对表达量。结果:Cur组细胞凋亡率、LC3Ⅱ/Ⅰ及Beclin1、E-cadherin蛋白相对表达量显著高于Control组,细胞迁移与侵袭数及Vimentin、BCL9、β-Catenin蛋白相对表达量显著低于Control组(P<0.05);Cur+3-MA组细胞凋亡率、LC3Ⅱ/Ⅰ及Beclin1、E-cadherin蛋白相对表达量显著低于Cur组,细胞迁移与侵袭数及Vimentin、BCL9、β-Catenin蛋白相对表达量显著高于Cur组(P<0.05);Cur+OE-BCL9组细胞凋亡率、LC3Ⅱ/Ⅰ及Beclin1、E-cadherin蛋白相对表达量显著低于Cur+VEC组,细胞迁移与侵袭数及Vimentin、BCL9、β-Catenin蛋白相对表达量显著高于Cur+VEC组(P<0.05);Cur+Sh-BCL9组细胞凋亡率、LC3Ⅱ/Ⅰ及Beclin1、E-cadherin蛋白相对表达量显著高于Cur+Sh-NC组,细胞迁移与侵袭数及Vimentin、BCL9、β-Catenin蛋白相对表达量显著低于Cur+Sh-NC组(P<0.05)。结论:姜黄素能通过抑制β-Catenin/BCL9信号通路,诱导细胞自噬,抑制HepG2细胞恶性生物学行为。Objective:To investigate the effect of curcumin(Cur)on autophagy and biological behavior of hepatocellular carcinoma cells HepG2 by regulatingβ-Catenin/BCL9 pathway.Methods:HepG2 cells were divided into control group,Cur group(20.0μmol/L Cur),Cur+autophagy inhibitor group(20.0μmol/L Cur+5.0 mmol/L 3-MA),Cur+plasmid control group(20.0μmol/L Cur+VEC),Cur+BCL9 overexpression group(20.0μmol/L Cur+OE-BCL9),Cur+shRNA lentiviral vector negative control group(20.0μmol/L Cur+Sh-NC)and Cur+shRNA Bcl9 lentiviral vector group(20.0μmol/L Cur+Sh-BCL9).The apoptosis,migration and invasion of HepG2 cells were detected,and the formation and level of autophagosomes were observed.Western blotting was used to detect the relative expression of autophagy(LC3Ⅱ/Ⅰ,Beclin1),epithelial-mesenchymal transition(Vimentin,E-cadherin),β-Catenin/BCL9 pathway(BCL9,β-Catenin)related proteins.Results:The apoptosis rate,the relative expression of LC3Ⅱ/Ⅰ,Beclin1 and E-cadherin protein in the Cur group were significantly higher than those in the control group,and the number of cell migration and invasion and the relative expression of Vimentin,BCL9 andβ-Catenin protein were significantly lower than those in the control group(P<0.05).The apoptosis rate,LC3Ⅱ/Ⅰand the relative expression of Beclin1 and E-cadherin protein in Cur+3-MA group were significantly lower than those in Cur group,and the number of cell migration and invasion and the relative expression of Vimentin,BCL9 andβ-Catenin protein were significantly higher than those in Cur group(P<0.05).The apoptosis rate and the relative expression of LC3Ⅱ/Ⅰ,Beclin1 and E-cadherin protein in Cur+OE-BCL9 group were significantly lower than those in Cur+VEC group,while the number of cell migration and invasion and the relative expression of Vimentin,BCL9 andβ-Catenin protein were significantly higher than those in Cur+VEC group(P<0.05).The apoptosis rate,LC3Ⅱ/Ⅰ,Beclin1 and E-cadherin protein expression in Cur+Sh-BCL9 group were significantly higher than those in Cur+Sh-NC gr

关 键 词：姜黄素 肝癌细胞 β-Catenin/BCL9信号通路 细胞自噬 HepG2细胞 

分 类 号：R285.5[医药卫生—中药学]