High Sensitivity to Cholic Acid-induced Colonic Tumorigenesis Makes Female PIRC Rats (F344/NTac-Apc
Adenomatous Polyposis Coli
/ complications
Animals
Apoptosis
/ genetics
Cell Proliferation
Cell Transformation, Neoplastic
/ chemically induced
Cholic Acid
/ adverse effects
Colorectal Neoplasms
/ etiology
Disease Models, Animal
Female
Gene Expression
Genes, APC
Mutation
Precancerous Conditions
Rats
Apc gene
Bile acids
PIRC rat
colon tumorigenesis
preneoplastic lesions
Journal
Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988
Informations de publication
Date de publication:
Sep 2019
Sep 2019
Historique:
received:
24
07
2019
revised:
23
08
2019
accepted:
27
08
2019
entrez:
15
9
2019
pubmed:
15
9
2019
medline:
27
9
2019
Statut:
ppublish
Résumé
Rats of the adenomatous polyposis coli (Apc)-mutated female polyposis in rat (PIRC) (F344/NTac-Apc To test this possibility, we treated such rats with the bile acid (BA) cholic acid (CA) (0.3% w/w in the diet), known to promote CRC, and assessed tumorigenesis. Precancerous colonic lesions (mucin-depleted foci) and intestinal tumors were dramatically increased in CA-treated rats compared to controls (p<0.01). Colon mucosa proliferation was higher and apoptosis lower than those in controls. Expression of nuclear receptor 1h4 (Nr1h4) gene [encoding for BA receptor farnesoid X receptor (FXR)], organic solute transporter beta (Ostb) and fatty acid-binding protein 6 (Fabp6), FXR-dependent BA transporters, were dramatically down-regulated in CA-treated rats. CA-increased tumorigenesis in female PIRC rats, with mechanisms involving increased proliferation, reduced apoptosis and marked down-regulation of genes controlling BA homeostasis. Since BAs have been implicated in CRC, we suggest that female PIRC rats can be used to identify CRC-promoting agents.
Sections du résumé
BACKGROUND/AIM
OBJECTIVE
Rats of the adenomatous polyposis coli (Apc)-mutated female polyposis in rat (PIRC) (F344/NTac-Apc
MATERIALS AND METHODS
METHODS
To test this possibility, we treated such rats with the bile acid (BA) cholic acid (CA) (0.3% w/w in the diet), known to promote CRC, and assessed tumorigenesis.
RESULTS
RESULTS
Precancerous colonic lesions (mucin-depleted foci) and intestinal tumors were dramatically increased in CA-treated rats compared to controls (p<0.01). Colon mucosa proliferation was higher and apoptosis lower than those in controls. Expression of nuclear receptor 1h4 (Nr1h4) gene [encoding for BA receptor farnesoid X receptor (FXR)], organic solute transporter beta (Ostb) and fatty acid-binding protein 6 (Fabp6), FXR-dependent BA transporters, were dramatically down-regulated in CA-treated rats.
CONCLUSION
CONCLUSIONS
CA-increased tumorigenesis in female PIRC rats, with mechanisms involving increased proliferation, reduced apoptosis and marked down-regulation of genes controlling BA homeostasis. Since BAs have been implicated in CRC, we suggest that female PIRC rats can be used to identify CRC-promoting agents.
Identifiants
pubmed: 31519566
pii: 39/9/4673
doi: 10.21873/anticanres.13649
doi:
Substances chimiques
Cholic Acid
G1JO7801AE
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4673-4679Informations de copyright
Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.