Glycyrrhetinic Acid Inhibits Malignant Progression of Hepatocellular Carcinoma by Inducing Autophagy and Regulating Macrophage Polarization via the TGF-β1/SMAD Pathway
| Author | Youjin Wang | en |
| Author | Huiyun Guan | en |
| Author | Peibei Duan | en |
| Issued Date | 2026-12-31 | en |
| Abstract | Background: Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies, and its poor prognosis is primarily attributed to its complex tumor microenvironment (TME). Glycyrrhetinic acid (GA) possesses potent anti-tumor properties, but its mechanisms of action and molecular targets within the HCC microenvironment remain to be thoroughly explored. Methods: Methods: This study employed HCC cell lines and a mouse xenograft model. In vitro experiments, we evaluated the effects of GA on HCC cell proliferation, migration, invasion, and apoptosis, and analyzed its role in M2 macrophage polarization within a co-culture system. Interventions using the autophagy inhibitor chloroquine (CQ) and the TGF-β1 signaling pathway activator SRI-011381 were performed, and the expression levels of autophagy markers, M1/M2 macrophage markers, and TGF-β1/SMAD pathway-related proteins were detected. In vivo experiments, we assessed the effects of GA on tumor progression, autophagy processes, and M2 macrophage infiltration. Results: In vitro, GA significantly inhibited malignant behaviors of HCC cells and promoted their apoptosis and autophagy. Furthermore, GA treatment effectively blocked M2 macrophage polarization and their pro-tumorigenic function in the co-culture system, an effect that was significantly reversed by CQ. Regarding the molecular mechanism, GA was found to inhibit the activation of the TGF-β1/SMAD axis, and the TGF-β1 pathway activator SRI-011381 reversed GA's induction of autophagy and inhibition of M2 polarization. In animal experiments, GA treatment significantly suppressed tumor growth and promoted cell apoptosis; concurrently, GA promoted autophagy and reduced M2 macrophage infiltration in tumor tissues. All these effects were reversible by SRI-011381. Conclusions: Glycyrrhetinic acid inhibits HCC malignant progression by suppressing the TGF-β1/SMAD axis, inducing autophagy in HCC cells, and inhibiting M2 macrophage polarization | en |
| DOI | https://doi.org/10.5812/hepatmon-169009 | en |
| URI | https://brieflands.com/journals/hepatmon/articles/169009 | en |
| Keyword | Glycyrrhetinic Acid | en |
| Keyword | Hepatocellular Carcinoma | en |
| Keyword | Macrophage Polarization | en |
| Keyword | TGF-β1/SMAD | en |
| Keyword | Autophagy | en |
| Publisher | Brieflands | en |
| Title | Glycyrrhetinic Acid Inhibits Malignant Progression of Hepatocellular Carcinoma by Inducing Autophagy and Regulating Macrophage Polarization via the TGF-β1/SMAD Pathway | en |
| Type | Research Article | en |