Alisol B 23-Acetate Increases the Antitumor Effect of Bufalin on Liver Cancer through Inactivating Wnt/-Catenin Axis.

Objective: Liver cancer seriously threatens the health of people. Meanwhile, it has been reported that bufalin could act as an inhibitor in liver cancer. In addition, alisol B 23-acetate is a natural product derived from which has an antitumor effect. In this study, we aimed to explore whether alisol B 23-acetate could increase the antitumor effect of bufalin on liver cancer.

Methods: In order to detect the effect of alisol B 23-acetate in combination with bufalin on liver cancer, human liver cancer SMMC-7721 and MHCC97 cells were used as subjects. Bufalin and alisol B 23-acetate were performed on cells. Cell viability was tested by MTT assay. In addition, flow cytometry was performed to assess the cell apoptosis. Autophagy-related protein levels were tested by western blotting.

Results: The data revealed that bufalin significantly decreased the viability of liver cancer cells, and the inhibitory effect was further increased by alisol B 23-acetate. In addition, alisol B 23-acetate notably enhanced the apoptotic effect of bufalin on liver cancer cells through mediation of Mcl-1, Bax, Bcl-2, and cleaved caspase-3. Meanwhile, alisol B 23-acetate in combination with bufalin induced the autophagy in liver cancer cells through mediation of Beclin-1 and p62. Furthermore, alisol B 23-acetate in combination with bufalin significantly downregulated the level of GSK-3 and increased the expression of -catenin in liver cancer cells.

Conclusion: In summary, these findings provide the first evidence that alisol B 23-acetate improves the anticancer activity of bufalin on liver cancer through activation of the Wnt/-catenin axis, and these outcomes might shed new lights on exploring the new methods against liver cancer.