Abstract
BackgroundHepatocellular 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.MethodsProliferation, wound healing, transwell-migration/invasion and adhesion assays were performed in HCCLM3 and HepG2 cell lines. The protein levels of pAKT, AKT, pGSK3β, GSK3β, pβ-catenin, β-catenin, E-cadherin, MMP-9, and MMP-2 were measured by western blot analysis. E-Cadherin and β-catenin expression levels were also evaluated by immunofluorescence.ResultsBufalin inhibited hepatoma cell proliferation, migration, invasion and adhesion. In addition, treatment with bufalin significantly decreased the levels of pAKT, pGSK3β, MMP-9, and MMP-2, while increasing the levels of GSK3β and E-cadherin and suppressing the nuclear translocation of β-catenin.ConclusionsBufalin is a potential anti-HCC therapeutic candidate through its inhibition of the AKT/GSK3β/β-catenin/E-cadherin signaling pathway. Further studies with bufalin are warranted in patients with HCC, especially those with the disease at advanced stages.
Highlights
Hepatocellular carcinoma (HCC) is a common and aggressive cancer, and the treatment options are limited for patients with advanced HCC
Immunofluorescence The expression levels of β-catenin and E-cadherin in bufalin-treated HCCLM3 and HepG2 cells were evaluated by immunofluorescence
Cells were grown on glass cover slips to 60–80% confluence, and fixed, Figure 2 Inhibition curves of bufalin on hepatoma cell proliferation
Summary
Hepatocellular carcinoma (HCC) is a common and aggressive cancer, and the treatment options are limited for patients with advanced HCC. The major digoxin-like component of the traditional Chinese medicine Chansu, exhibits significant anti-tumor activities in many tumor cell lines. 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. Initially recorded more than 1000 years ago, is a well-known traditional Chinese medicine widely used in clinical cancer therapy in China [7,8]. It was demonstrated that bufalin caused apoptosis of gastric cancer cells by inhibition of the AKT signaling pathway via CBL-B and CBL-C [10]. AKT ( known as PKB) is a master regulator that when activated by phosphorylation modifies at least 10 major regulatory proteins and initiates many pathways in tumor cells [11]. AKT is instrumental in angiogenesis and epithelial mesenchymal transitions during tumorigenesis [13,14]
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