Obesity reduces the anticancer effect of AdipoRon against orthotopic pancreatic cancer in diet-induced obese mice.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
03 02 2021
03 02 2021
Historique:
received:
07
05
2020
accepted:
12
01
2021
entrez:
4
2
2021
pubmed:
5
2
2021
medline:
16
11
2021
Statut:
epublish
Résumé
The antidiabetic adiponectin receptor agonist AdipoRon has been shown to suppress the tumour growth of human pancreatic cancer cells. Because obesity and diabetes affect pancreatic cancer progression and chemoresistance, we investigated the effect of AdipoRon on orthotopic tumour growth of Panc02 pancreatic cancer cells in DIO (diet-induced obese) prediabetic mice. Administration of AdipoRon into DIO mice fed high-fat diets, in which prediabetic conditions were alleviated to some extent, did not reduce either body weight or tumour growth. However, when the DIO mice were fed low-fat diets, body weight and the blood leptin level gradually decreased, and importantly, AdipoRon became effective in suppressing tumour growth, which was accompanied by increases in necrotic areas and decreases in Ki67-positive cells and tumour microvessels. AdipoRon inhibited cell growth and induced necrotic cell death of Panc02 cells and suppressed angiogenesis of endothelial MSS31 cells. Insulin and IGF-1 only slightly reversed the AdipoRon-induced suppression of Panc02 cell survival but had no effect on the AdipoRon-induced suppression of MSS31 cell angiogenesis. Leptin significantly ameliorated AdipoRon-induced suppression of angiogenesis through inhibition of ERK1/2 activation. These results suggest that obesity-associated factors weaken the anticancer effect of AdipoRon, which indicates the importance of weight loss in combating pancreatic cancer.
Identifiants
pubmed: 33536560
doi: 10.1038/s41598-021-82617-2
pii: 10.1038/s41598-021-82617-2
pmc: PMC7859201
doi:
Substances chimiques
AdipoRon
0
Piperidines
0
Receptors, Adiponectin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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