[摘 要] 目的：探讨甘草次酸（GA）调节β-连环蛋白（β-catenin）/转录因子4（TCF4）信号通路对肝细胞癌SMMC-7721细胞增 殖、迁移、侵袭及上皮间质转化（EMT）的影响及其机制。方法：以HCC细胞SMMC-7721为研究对象，将其随机分为对照、 L-GA、M-GA、H-GA组（50、100、200 μmol/L GA）、GA + LiCl组（200 μmol/L GA + 40 μmol/L β-catenin激活剂LiCl）。采用平板克 隆实验、Transwell实验、流式细胞术检测GA对SMMC-7721细胞增殖、迁移和侵袭及细胞凋亡的影响，WB法检测GA对SMMC 7721细胞中β-catenin/TCF4通路蛋白（β-catenin、TCF4）和EMT相关蛋白（E-cadherin、vimentin）表达的影响。构建SMMC-7721细 胞裸鼠移植瘤模型，观察GA对荷瘤裸鼠移植瘤生长及β-catenin、TCF4蛋白表达的影响。结果：与对照组相比，L-GA、 M-GA、H-GA组SMMC-7721细胞克隆数、迁移和侵袭数、β-catenin、TCF4、vmentin蛋白表达均显著降低（均P < 0.05），细胞凋亡 率、E-cadherin蛋白表达均升高（均P < 0.05）；与H-GA组相比，GA + LiCl组细胞克隆数、迁移和侵袭数、β-catenin、TCF4、vimentin 蛋白表达均显著升高（均P < 0.05），细胞凋亡率、E-cadherin蛋白表达均显著降低（均P < 0.05）。荷瘤裸鼠模型实验显示，GA组裸 鼠移植瘤质量和体积、β-catenin和TCF4蛋白阳性率均显著低于对照组（均P < 0.05）。结论：GA显著抑制SMMC-7721细胞的增 殖、迁移、侵袭和EMT进程，进而抑制HCC的进展，其机制可能是通过抑制β-catenin/TCF4信号通路实现的。

[Abstract] Objective: To investigate the effects and mechanisms of glycyrrhetinic acid (GA) on the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of hepatocellular carcinoma SMMC-7721 cells by regulating the β-catenin/transcription factor 4 (TCF4) signaling pathway. Methods: HCC cells SMMC-7721 were randomly separated into the control, L-GA, M-GA, H-GA groups (50, 100, 200 μmol/L GA) and the GA + LiCl group (200 μmol/L GA + 40 μmol/L β-catenin activator LiCl). The effects of GA on the proliferation, migration, invasion and apoptosis of SMMC-7721 cells were detected by plate cloning, Transwell experiment and flow cytometry. WB was applied to detect the effects of GA on the expressions of β-catenin/TCF4 signaling pathway proteins (β-catenin、TCF4) and EMT (E-cadherin, vimentin)-related proteins in SMMC-7721 cells. The model of SMMC-7721 cell transplanted tumor in nude mice was established to observe the effects of GA on the growth of transplanted tumor and the expressions of β-catenin and TCF4 proteins. Results: Compared with the control group, SMMC-7721 cell clonal number, migration and invasion numbers, β-catenin, TCF4 and vmentin protein expressions in the L-GA, M-GA and H-GA groups decreased significantly (all P < 0.05), while the apoptosis rate and the expression of E-cadherin protein increased (all P < 0.05). Compared with the H-GA group, the numbers of clones, migration and invasion, β-catenin, TCF4 and vimentin protein expressions in the GA + LiCl group increased significantly (all P < 0.05), while the apoptosis rate and E-cadherin protein expression decreased significantly (all P < 0.05). Tumor-bearing nude mouse model experiment showed that the tumor weight and volume and the positive rates of β-catenin and TCF4 proteins in the GA group were significantly lower than those in the control group (all P < 0.05). Conclusion: GA can significantly inhibit the proliferation,migration, invasion, and the EMT process of SMMC-7721 cells, thereby inhibiting the progression of HCC. Its mechanism may be achieved by inhibiting the β-catenin/TCF4 signaling pathway.

2020年度武汉市临床医学科研项目（No. WZ20B02）