【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。更多还原

【Abstract】 Objective: To investigate the effect of curcumin(Cur) on autophagy and biological behavior of hepatocellular carcinoma cells HepG2 by regulating β-Catenin/BCL9 pathway. Methods: HepG2 cells were divided into control group, Cur group(20.0 μmol/L Cur), Cur+autophagy inhibitor group(20.0 μmol/L Cur+5.0 mmol/L 3-MA),Cur+plasmid control group(20.0 μmol/L Cur+VEC), Cur+BCL9 overexpression group(20.0 μmol/L Cur+OE-BCL9),Cur+shRNA lentiviral vector negative control group(20.0 μmol/L Cur+Sh-NC) and Cur+shRNA Bcl9 lentiviral vector group(20.0 μmol/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 and β-Catenin protein were significantly lower than those in the control group(P<0.05). The apoptosis rate, LC3Ⅱ/Ⅰ and 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 and β-Catenin protein were significantly higher than those in Cur group(P<0.05). The apoptosis rate and the relative expression of LC3 Ⅱ/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 and β-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 group, and the number of cell migration and invasion and the relative expression of Vimentin, BCL9 and β-Catenin protein were significantly lower than those in Cur+Sh-NC group(P<0.05). Conclusion: Curcumin can induce autophagy and inhibit the malignant biological behavior of HepG2 cells by inhibiting β-Catenin/BCL9 signaling pathway.更多还原