Berbamine Exerts an Anti-oncogenic Effect on Pancreatic Cancer by Regulating Wnt and DNA Damage-related Pathways

Abstract

Objective: This study aimed to determine the effects of berbamine on pancreatic cancer as well as the underlying mechanisms. Methods: The pancreatic cancer cells were treated with different concentrations of berbamine and then subjected to cell viability assay, colony formation assay, cell cycle analysis, and apoptosis detection. Western blotting and immunofluorescence analyses were performed to investigate the mechanisms underlying the biological effects of berbamine on the pancreatic cancer cells. Furthermore, the in vivo anti-pancreatic cancer effect of berbamine was examined using a mouse xenograft model. Results: Berbamine significantly inhibited the proliferation and colony-forming ability of BxPC3 and PANC-1 pancreatic cancer cells while inducing a cell cycle arrest and apoptosis. Moreover, berbamine decreased the expression of β- catenin and phosphorylation of GSK3β but increased the expression of γ-H2AX and 53BP1. Meanwhile, in vivo studies revealed that berbamine attenuated the growth of xenograft tumors derived from PANC-1 cells. Notably, berbamine treatment led to an increase in the expression of Cleaved Caspase 3 and γ-H2AX, as well as a decrease in the expression of Ki-67 and β-catenin in the tumor xenografts. Conclusion: Berbamine exerts an anti-pancreatic cancer effect, possibly by regulating Wnt and DNA damage-related pathways, suggestive of its therapeutic potential for pancreatic cancer.