Britannin inhibits hepatocellular carcinoma development and metastasis through the GSK-3β/β-catenin signaling pathway

作者：Qinwei Lu, Junlin Zhu, Linxin Teng, Cuihua Chen, Lei Bi, Weiping Chen · 发表于：Phytomedicine · 年份：2024 · DOI：10.1016/j.phymed.2024.156126 · 被引用次数：13 · 研究领域：Wnt/β-catenin signaling in development and cancer、NF-κB Signaling Pathways、Plant chemical constituents analysis

BACKGROUND: Hepatocellular carcinoma (HCC) stands out as a significant contributor to cancer-related death. Traditional Chinese Medicine (TCM) offers several advantages in the treatment of HCC. Britannin, a pivotal compound in Inulae Flos, has demonstrated pharmacological effects against various cancers, yet research on its specific anti-HCC effects remains limited. PURPOSE: This study aims to explore the anti-HCC effects of britannin and its underlying mechanism. METHODS: MTT assay, clone formation assay and flow cytometry were utilized to detect the cell activity, proliferation ability and apoptosis of britannin against HCC cell lines. Cell migration and invasion abilities of HCC cell lines treated with britannin were evaluated by wound-healing assay and transwell migration and invasion assay. H22 xenografted tumor mouse model was constructed and britannin treatment was performed to observe the effect of britannin on HCC tumors. The expression levels of liver cancer biomarkers AFP, AFP-L3, APT and TGF-β were detected by Elisa, and the histopathology was observed by HE staining. Network pharmacology and molecular docking were used to predict the possible signaling pathway of anti-HCC effect of britannin. The surface plasmon resonance (SPR) experiment was used to verify the interaction between britannin and proteins. The cell kinase activity function experiment was employed to detect the effect of britannin on enzyme activity. RT-qPCR and Western-Blot were used to verify the ...