Wogonoside Inhibits Prostate Cancer Cell Growth and Metastasis via Regulating Wnt/beta-Catenin Pathway and Epithelial-Mesenchymal Transition

摘要

Background: Wogonoside, an effective component of Scutellaria baicalensis extract, has recently become a hot topic for its newly discovered anticancer efficacy, but the underlying pharmacological mechanism is still unclear. In this study, we tested the inhibitory effects of wogonoside in human prostate cancer PC3 cells in vitro and vivo. Methods: The effects of wogonoside on cell viability, cycle progression, invasion, migration, and apoptosis were assessed in vitro. The levels of proteins in related signaling pathways were detected by western blotting assay. Finally, nude mouse tumorigenicity assay was conducted to detect the anticancer effect of wogonoside in vivo. Results: Wogonoside inhibited cell viability, invasive and migratory ability in a time- and dose-dependent manner. Flow cytometry indicated that wogonoside could induce cell apoptosis and S phase cell-cycle arrest. Mechanically, wogonoside suppressed the Wnt/beta-catenin signaling pathway, and the level of p-glycogen synthase kinase-3 beta (GSK-3 beta; Ser(9)) was inhibited by wogonoside. The epithelial-mesenchymal transition (EMT) process was also reversed in PC3 cell line after wogonoside treatment. In vivo experiments showed that wogonoside inhibited tumor growth in xenograft mouse models. Conclusion: These findings revealed that wogonoside could suppress Wnt/beta-catenin pathway and reversing the EMT process in PC3 cells. GSK-3 beta acts as a tumor suppressor in prostate cancer. Wogonoside may serve as an effective agent for treating prostate cancer.