Glycyrrhetinic acid inhibits the malignant biological behavior of hepatocellular carcinoma SMMC-7721 cells through the β-catenin/TCF4 signaling pathway
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Abstract:
[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.