Pharmacological inhibition and reversal of pancreatic acinar ductal metaplasia.

ABSTRACT: Pancreatic acinar cells display a remarkable degree of plasticity and can dedifferentiate into ductal-like progenitor cells by a process known as acinar ductal metaplasia (ADM). ADM is believed to be one of the earliest precursor lesions toward the development of pancreatic ductal adenocarcinoma and maintaining the pancreatic acinar cell phenotype suppresses tumor formation. The effects of a novel pStat3 inhibitor (LLL12B) and the histone deacetylase (HDAC) inhibitor trichostatin A (TSA) were investigated using 3-D cultures from p48^Cre/+ and p48^Cre/+LSL-Kras^G12D/+ (KC) mice. LLL12B and TSA inhibited ADM in both KC and p48^Cre/+ mouse pancreatic organoids. Furthermore, treatment with LLL12B or TSA on dedifferentiated acini from p48^Cre/+

SUBMITTER: da Silva L 

PROVIDER: S-EPMC9440259 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature