PHARMACOLOGICAL INHIBITION AND REVERSAL OF PANCREATIC ACINAR DUCTAL METAPLASIA

Acinar ductal metaplasia (ADM), is believed to be one of the earliest precursor lesions towards the development of pancreatic ductal adenocarcinoma, and maintaining the pancreatic acinar cell phenotype suppresses tumor formation. We report that pStat3 and HDAC inhibition can attenuate ADM in vitro and TSA treatment reverses the dedifferentiated phenotype to one that is more acinar. Our findings suggest that pharmacological inhibition or reversal of pancreatic ADM represents a potential therapeutic strategy for blocking ductal reprogramming of acinar cells. Following KC mouse acini undergoing ADM for 2 days, 500 nM of TSA or LLL12B was added to the cultures for an additional 2 days. Cells from the LLL12B, TSA, or day 4 untreated controls cells in triplicate were subjected to whole transcriptome sequencing.