Activation of peroxisome proliferator-activated receptor-gamma inhibits tumor growth by negatively regulating nuclear factor-[kappa]B activation in patients with hepatocellular carcinoma

Background The prognosis of advanced hepatocellular carcinoma (HCC) is poor because of its rapid progression. Peroxisome proliferator-activated receptor-gamma (PPAR[gamma]) is known to inhibit tumor growth in vitro; however, the behavior of PPAR[gamma] in clinical cases of HCC remains uncertain. Met...

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Bibliographic Details
Published in:Journal of hepato-biliary-pancreatic sciences 2016-09, Vol.23 (9), p.574
Main Authors: Nojima, Hiroyuki, Kuboki, Satoshi, Shinoda, Kimio, Shimizu, Hiroaki, Ohtsuka, Masayuki, Kato, Atsushi, Yoshitomi, Hideyuki, Furukawa, Katsunori, Takayashiki, Tsukasa, Miyazaki, Masaru
Format: Article
Language:English
Subjects:
Cell cycle
Cell growth
Genes
Ligands
Liver cancer
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Summary:Background The prognosis of advanced hepatocellular carcinoma (HCC) is poor because of its rapid progression. Peroxisome proliferator-activated receptor-gamma (PPAR[gamma]) is known to inhibit tumor growth in vitro; however, the behavior of PPAR[gamma] in clinical cases of HCC remains uncertain. Methods Surgical specimens were collected from 104 HCC patients. The anti-neoplastic effects of PPAR[gamma] were evaluated. Results PPAR[gamma] and its ligand expression were increased in some cases of HCC. When HCC patients were divided into two groups, tumor size was larger in patients with low PPAR[gamma] expression. Moreover, low PPAR[gamma] expression in HCC was an independent predictor of poorer prognosis. PPAR[gamma] expression was positively correlated with PPAR[gamma] activation and negatively correlated with NF-[kappa]B activation in HCC. PPAR[gamma] activation inhibited cell proliferation by inducing cell cycle arrest, through increased expression of p27(kip1) and decreased expression of cyclin D1 and interleukin-8. When HCC cells were treated with PPAR[gamma] ligands, PPAR[gamma] activation was increased and cell proliferation was inhibited in a dose-dependent manner. In contrast, PPAR[gamma] ligands negatively regulated NF-[kappa]B activation. Conclusions Activation of PPAR[gamma] induces cell cycle arrest and inhibits tumor progression by negatively regulating NF-[kappa]B activation in HCC. Therefore, PPAR[gamma] is an important endogenous regulator of HCC progression, and is a potential therapeutic target for HCC.
ISSN:1868-6974
1868-6982
DOI:10.1002/jhbp.378