Berberine inhibits the proliferation of pancreatic cancer cells by targeting pancreatic cancer stem cells through regulating EMT signaling pathway

Pancreatic ductal adenocarcinoma(PDAC)is universally acknowledged as the cancer with the highest mortality rate.Berberine has high medicinal value and has been used as an anti-cancer agent.Hence the purpose of this study was to investigate the anti-cancer effect of berberine in PDAC.Berberine was shown to have a selective anti-cancer effect on PDAC by MTT assay in vitro.Pancreatic cancer stem cells(PCSCs),regulated by epithelial-mesenchymal transition(EMT),could promote the proliferation of PDAC cells.However,berberine suppressed the proliferation and stemness of PCSCs through immunofluorescence staining,stem cell sphere assays and so forth in vitro.In vivo,berberine reduced tumor size and decreased the expression levels of Ki67,a marker of cellular proliferation,in orthotopic pancreatic tumors.In addition,berberine inhibited the EMT signaling pathway by RT-PCR and Western blotting methods both in vitro and in vivo.Our study indicates that berberine inhibits the proliferation of PDAC cells both in vivo and in vitro.The mechanism of the anti-cancer effect of berberine likely involves the inhibition of EMT.Therefore,berberine may be a novel antineoplastic drug with clinical efficacy in PDAC.