Berberine inhibits pancreatic intraepithelial neoplasia by inhibiting glycolysis via the adenosine monophosphate -activated protein kinase pathway

Abstract

Most cases of pancreatic cancer develop in patients with chronic pancreatitis (CP). Berberine is natural product that exhibits anti-tumor effects in various types of cancer and is used in traditional Chinese medicine. In this study, we demonstrated that berberine inhibited the development of pancreatic intraepithelial neoplasia (PanIN) in an in vivo CP model and an in vitro acinar-to-ductal metaplasia model. As berberine may inhibit glycolysis during the development of PanIN, we measured indicators of glycolysis. Quantitative reverse transcription polymerase chain reaction and western blotting assays revealed that berberine activated the adenosine monophosphate-activated protein kinase (AMPK) pathway. This demonstrated that berberine suppressed glycolysis by targeting AMPK, a key metabolic sensor. Furthermore, berberine acted via the AMPK–hypoxia-inducible factor 1 alpha pathway to achieve suppression of PanIN. These findings show that berberine is a potential therapeutic candidate for preventing the progression of CP to PanIN.