Effects of a DPP4 Inhibitor on Progression of NASH-related HCC and the p62/ Keap1/Nrf2-Pentose Phosphate Pathway in a Mouse Model.
Antidiabetic agent
Dipeptidyl peptidase-4
Hepatoma
Nonalcoholic fatty liver disease
Pentose phosphate shunt
Journal
Liver cancer
ISSN: 2235-1795
Titre abrégé: Liver Cancer
Pays: Switzerland
ID NLM: 101597993
Informations de publication
Date de publication:
Oct 2019
Oct 2019
Historique:
received:
13
01
2018
accepted:
29
06
2018
entrez:
27
11
2019
pubmed:
27
11
2019
medline:
27
11
2019
Statut:
ppublish
Résumé
Diabetes mellitus is a risk factor for hepatocellular carcinoma (HCC) in patients with nonalcoholic steatohepatitis (NASH). Dipeptidyl peptidase-4 inhibitor (DPP4i), an antidiabetic agent, is reported to affect cell proliferation. We aimed to investigate the effects of DPP4i on the progression of NASH-related HCC and its metabolic pathway in a mouse model. A mouse model of NASH-related HCC was used in this study. Eight-week-old mice were administered either DPP4i (sitagliptin 30 mg/kg/day; DPP4i group; The number and volume of HCC were significantly lower in the DPP4i group than in the control group (1.8 ± 1.2 vs. 4.5 ± 1.7/liver, We demonstrated that DDP4i prevented the progression of NASH-related HCC in a mouse model. Furthermore, metabolome analysis revealed that DDP4i downregulated the pentose phosphate pathway with suppression of the p62/Keap1/Nrf2 pathway. Thus, DDP4i may prevent tumor progression through inhibition of metabolic reprogramming in NASH-related HCC.
Sections du résumé
BACKGROUND AND AIMS
OBJECTIVE
Diabetes mellitus is a risk factor for hepatocellular carcinoma (HCC) in patients with nonalcoholic steatohepatitis (NASH). Dipeptidyl peptidase-4 inhibitor (DPP4i), an antidiabetic agent, is reported to affect cell proliferation. We aimed to investigate the effects of DPP4i on the progression of NASH-related HCC and its metabolic pathway in a mouse model.
METHODS
METHODS
A mouse model of NASH-related HCC was used in this study. Eight-week-old mice were administered either DPP4i (sitagliptin 30 mg/kg/day; DPP4i group;
RESULTS
RESULTS
The number and volume of HCC were significantly lower in the DPP4i group than in the control group (1.8 ± 1.2 vs. 4.5 ± 1.7/liver,
CONCLUSIONS
CONCLUSIONS
We demonstrated that DDP4i prevented the progression of NASH-related HCC in a mouse model. Furthermore, metabolome analysis revealed that DDP4i downregulated the pentose phosphate pathway with suppression of the p62/Keap1/Nrf2 pathway. Thus, DDP4i may prevent tumor progression through inhibition of metabolic reprogramming in NASH-related HCC.
Identifiants
pubmed: 31768345
doi: 10.1159/000491763
pii: lic-0008-0359
pmc: PMC6873068
doi:
Types de publication
Journal Article
Langues
eng
Pagination
359-372Informations de copyright
Copyright © 2018 by S. Karger AG, Basel.
Déclaration de conflit d'intérêts
All authors disclose no conflicts.
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