The PPARgamma agonist pioglitazone inhibits early neoplastic occurrence in the rat liver.

Details

Serval ID
serval:BIB_92DB3034EFC1
Type
Article: article from journal or magazin.
Collection
Publications
Title
The PPARgamma agonist pioglitazone inhibits early neoplastic occurrence in the rat liver.
Journal
European Journal of Cancer (oxford, England : 1990)
Author(s)
Borbath I., Leclercq I., Moulin P., Sempoux C., Horsmans Y.
ISSN
0959-8049 (Print)
ISSN-L
0959-8049
Publication state
Published
Issued date
2007
Peer-reviewed
Oui
Volume
43
Number
11
Pages
1755-1763
Language
english
Notes
Publication types: Journal ArticlePublication Status: ppublish
Abstract
Hepatocellular carcinoma (HCC) is increasing worldwide and is the fifth main cause of cancer-related death. HCC develops on a preneoplastic organ, the cirrhotic liver. Therefore, chemoprevention could play a role in the therapy of HCC. We evaluated the preventive effects of pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, on the induction of early carcinogenic events. We monitored pre-neoplastic foci induced by a two-stage initiation/promotion model of hepatocarcinogenesis in rats, using diethylnitrosamine and acetylaminofluorene. Pioglitazone treatment was initiated the day after the first diethylnitrosamine injection. By quantitative morphometry and Western blot, we showed that pioglitazone significantly decreases the size of pre-neoplastic foci. Analysis of proliferation and apoptosis, assessed by immunohistochemistry, demonstrated decreased proliferation but no effect on cell death in rats treated with pioglitazone. These events were associated with an increased expression of the cyclin-dependent kinase inhibitor p27(kip1), compared to the non treated group. In conclusion, pioglitazone inhibits early carcinogenic transformation in a two-step rat model. As pioglitazone has a low toxicity profile, we believe it would be interesting to evaluate its effect in chemoprevention of HCC in humans in a clinical setting.
Keywords
2-Acetylaminofluorene/toxicity, Animals, Anticarcinogenic Agents/therapeutic use, Apoptosis, Blotting, Western, Carcinogens/toxicity, Carcinoma, Hepatocellular/prevention & control, Cell Proliferation/drug effects, Chemoprevention, Diethylnitrosamine/toxicity, Immunohistochemistry, Ki-67 Antigen, Liver Neoplasms/prevention & control, Male, PPAR gamma/antagonists & inhibitors, Rats, Rats, Wistar, Thiazolidinediones/therapeutic use
Pubmed
Web of science
Create date
20/10/2016 17:10
Last modification date
03/03/2018 19:33
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