Abstract

Background/Aims: Despite some improvement in patient prognosis, hepatocellular carcinoma (HCC) remains a prevalent malignant tumor with disappointingly low overall survival rates. This study aims to investigate the inhibitory effects of astragalus polysaccharides (APs) on the malignant biological behavior of HCC and its underlying mechanisms, aiming to provide new strategies and theoretical foundations for HCC treatment. Materials and Methods: The inhibitory effects of APs on HCC were assessed using animal models and in vitro experiments. In animal models, different doses of APs were tested for their anti-tumor efficacy. In vitro , CCK-8 and Transwell assays assessed APs effects on HCCLM3 and HuH7 cell malignancy. Western blot analyzed Wnt/β-catenin pathway proteins and epithelial–mesenchymal transition (EMT) markers in APs-treated HCC cells. Rescue experiments confirmed APs-mediated inhibition of HCC behavior via Wnt/β-catenin signaling. Results: Animal experiments demonstrated that APs could effectively inhibit HCC development, with its inhibitory effect becoming stronger as the dose of APs increased. The in vitro data revealed that APs primarily inhibited the Wnt/β-catenin signaling pathway by downregulating β-catenin and p-GSK3β levels while increasing p-β-catenin levels, thereby inhibiting HCC malignancy. APs also regulated the expression of vimentin, N-cadherin, and E-cadherin—EMT markers. Moreover, in vitro rescue experiments indicated that APs induced apoptosis in HCC cells and inhibited their migration and invasion, which could be counteracted by a Wnt/β-catenin pathway activator. Conclusion: APs effectively curb the growth, spread, and invasiveness of HCC cells by targeting the Wnt/β-catenin pathway, thereby opening up new possibilities for HCC treatment.