RESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) is a common and aggressive cancer, and the treatment options are limited for patients with advanced HCC. Bufalin, the major digoxin-like component of the traditional Chinese medicine Chansu, exhibits significant anti-tumor activities in many tumor cell lines. In the present study, we investigated the effect of bufalin on the inhibition of an AKT-related signaling pathway, and examined the relationship between regulatory proteins and anti-tumor effects in hepatoma cells. METHODS: Proliferation, wound healing, transwell-migration/invasion and adhesion assays were performed in HCCLM3 and HepG2 cell lines. The protein levels of pAKT, AKT, pGSK3ß, GSK3ß, pß-catenin, ß-catenin, E-cadherin, MMP-9, and MMP-2 were measured by western blot analysis. E-Cadherin and ß-catenin expression levels were also evaluated by immunofluorescence. RESULTS: Bufalin inhibited hepatoma cell proliferation, migration, invasion and adhesion. In addition, treatment with bufalin significantly decreased the levels of pAKT, pGSK3ß, MMP-9, and MMP-2, while increasing the levels of GSK3ß and E-cadherin and suppressing the nuclear translocation of ß-catenin. CONCLUSIONS: Bufalin is a potential anti-HCC therapeutic candidate through its inhibition of the AKT/GSK3ß/ß-catenin/E-cadherin signaling pathway. Further studies with bufalin are warranted in patients with HCC, especially those with the disease at advanced stages.