Targeting cholecystokinin-2 receptor for pancreatic cancer chemoprevention.

ABSTRACT: Gastrin signaling mediated through cholecystokinin-2 receptor (CCK2R) and its downstream molecules is altered in pancreatic cancer. CCK2R antagonists, YF476 (netazepide) and JNJ-26070109, were tested systematically for their effect on pancreatic intraepithelial neoplasia (PanIN) progression to pancreatic ductal adenocarcinoma (PDAC) in Kras^G12D mice. After dose selection using wild-type mice, six-week-old p48^Cre/+ -LSL-Kras^G12D (22-24 per group) genetically engineered mice (GEM) were fed AIN-76A diets containing 0, 250, or 500 ppm JNJ-26070109 or YF-476 for 38 weeks. At termination, pancreata were collected, weighed, and evaluated for PanINs and PDAC. Results demonstrated that control-diet-fed mice showed 69% (males) and 33% (females) incidence of PDAC. Adm

SUBMITTER: Mohammed A 

PROVIDER: S-EPMC6721979 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature