Therapeutic Effect And Mechanism Of Berberine In Pancreatic Cancer

Pancreatic cancer is a very aggressive malignant tumor with high mortality.The most common histological subtype of pancreatic cancer is pancreatic ductal adenocarcinoma(PDAC).The existing treatment is mainly surgery and postoperative chemotherapy.Gemcitabine is the first-line chemotherapy drug in clinical treatment of pancreatic cancer,but some patients with pancreatic cancer is not sensitive to gemcitabine.In addition,the other part is the patients who are sensitive to gemcitabine with long-term treatment also produce a certain resistance.Therefore,it is an urgent problem for us to find new effective drugs to treat pancreatic cancer.As a natural product,berberine also has good therapeutic effect on a variety of tumors,and its toxic and side effects are not obvious.However,whether it has the same therapeutic effect on pancreatic cancer is not clear at present.Therefore,this study will explore whether berberine has a therapeutic effect on pancreatic cancer and its possible mechanism of action.In this study,the effect of berberine on pancreatic cancer was investigated both in vitro and in vivo.The effect of berberine on pancreatic cancer was evaluated by MTT assay,animal model,tumor size comparison,H&E staining,Ki67 immunohistochemistry and other experiments.The effects of berberine on pancreatic cancer stem cells(PCSCs)were evaluated by tumor stem cell sphere formation,flow cytometry and dual immunofluorescence assay of CD44~+CD133~+,wound healing and Transwell assay.The regulation of berberine on EMT signaling pathway was evaluated by Real-time fluorescence quantitative PCR and Western Blot assay.The results showed that berberine could significantly inhibit the proliferation of pancreatic cancer cells,reduce the size of tumor in vivo,and inhibit the expression of tumor proliferation marker Ki67,suggesting that berberine inhibited pancreatic cancer both in vivo and in vitro.Secondly,berberine reduced the proportion of PCSCs(CD44~+CD133~+double positive cells)and inhibited the ability of PCSCs,suggesting that berberine can inhibit pancreatic cancer by suppressing the proliferation and ability of PCSCs.Finally,Real-time quantitative PCR and Western Blot assays showed that berberine up-regulated the expression of E-cadherin and down-regulated the expression of N-cadherin,Snail,Twist,Vimentin which are classic biomarkers of the EMT pathway.These results indicated that berberine could significantly inhibit EMT signaling pathway both in vivo and in vitro.In other words,berberine regulated PCSCs by inhibiting EMT signaling pathway,and finally inhibited PDAC.In conclusion,our results suggest that berberine could inhibit the development of pancreatic cancer both in vivo and in vitro,possibly through inhibiting EMT signaling pathway and affecting PCSCs,and thus inhibiting PDAC.These results provided a new theoretical basis for clinical treatment of pancreatic cancer.