Polydatin inhibits hepatocellular carcinoma via the AKT/STAT3-FOXO1 signaling pathway.

Abstract

Polydatin, extracted from Polygonum cuspidatum, is known for its anti-platelet aggregation and anti-inflammatory effects. However, studies on the association of polydatin with cancer are limited, particularly with regards to epithelial-mesenchymal transition (EMT)-associated migration and invasion of cancer cells. The purpose of the present study was to reveal the potential anticancer effects of polydatin on hepatocellular carcinoma (HCC) cells, particularly its effects on EMT. MTT assay was used to determine cell viability. Migration and invasion were evaluated through wound healing and transwell assays. Colony formation efficiency assay was conducted to detect proliferation. Flow cytometric analyses of apoptosis and cell cycle progression were performed following cells staining with Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) and PI alone, respectively. Western blotting was used to investigate relevant molecular mechanisms. The results indicated that polydatin inhibited proliferation via G2/M arrest, suppressed migration and invasion of HCC cells, and promoted their apoptosis. In addition, phosphorylated (p)-protein kinase B (AKT), p-Janus kinase 1 and p-signal transducer and activator of transcription 3 (STAT3) levels were decreased as polydatin concentrations increased, and forkhead box protein O1 (FOXO1) expression was upregulated. Furthermore, the expression levels of various markers of EMT were reversed following treatment with polydatin. In conclusion, the present study validated that polydatin may inhibit proliferation via G2/M arrest, and suppressed EMT-associated migration and invasion of HCC cells. The results also suggested that polydatin may promote HCC cell apoptosis by blocking the AKT/STAT3-FOXO1 signaling pathway.