β-Sitosterol suppresses hepatocellular carcinoma growth and metastasis via FOXM1-regulated Wnt/β-catenin pathway

beta-Sitosterol is a natural compound with demonstrated anti-cancer properties against various cancers. However, its effects on hepatocellular carcinoma (HCC) and the underlying mechanisms are not well understood. This study aims to investigate the impact of beta-sitosterol on HCC. In this study, we investigated the effects of beta-sitosterol on HCC tumour growth and metastasis using a xenograft mouse model and a range of molecular analyses, including bioinformatics, real-time PCR, western blotting, lentivirus transfection, CCK8, scratch and transwell assays. The results found that beta-sitosterol significantly inhibits HepG2 cell proliferation, migration and invasion both in vitro and in vivo. Bioinformatics analysis identifies forkhead box M1 (FOXM1) as a potential target for beta-sitosterol in HCC treatment. FOXM1 is upregulated in HCC tissues and cell lines, correlating with poor prognosis in patients. beta-Sitosterol downregulates FOXM1 expression in vitro and in vivo. FOXM1 overexpression mitigates beta-sitosterol's inhibitory effects on HepG2 cells. Additionally, beta-sitosterol suppresses epithelial-mesenchymal transition (EMT) in HepG2 cells, while FOXM1 overexpression promotes EMT. Mechanistically, beta-sitosterol inhibits Wnt/beta-catenin signalling by downregulating FOXM1, regulating target gene transcription related to HepG2 cell proliferation and metastasis. beta-Sitosterol shows promising potential as a therapeutic candidate for inhibiting HCC growth and metastasis through FOXM1 downregulation and Wnt/beta-catenin signalling inhibition.