Irbesartan overcomes gemcitabine resistance in pancreatic cancer by suppressing stemness and iron metabolism via inhibition of the Hippo/YAP1/c-Jun axis.

ABSTRACT:

Background

Chemoresistance is the main reason for the poor prognosis of pancreatic ductal adenocarcinoma (PDAC). Thus, there is an urgent need to screen out new targets and compounds to reverse chemotherapeutic resistance.

Methods

We established a bio-bank of human PDAC organoid models, covering a representative range of PDAC tumor subtypes. We screened a library of 1304 FDA-approved compounds to identify candidates efficiently overcoming chemotherapy resistance. The effects of the compounds were evaluated with a CellTiter-Glo-3D assay, organoid apoptosis assay and in vivo patient-derived xenograft (PDX), patient-derived organoid (PDO) and LSL-Kras^G12D/+; LSL-Trp53^R172H/+; Pdx1-Cre (KPC) genetically engineered mouse models. RNA-sequencing, genome editin

SUBMITTER: Zhou T 

PROVIDER: S-EPMC10157938 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature