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

作者：Nojima Hiroyuki; Kuboki Satoshi^*; Shinoda Kimio; Shimizu Hiroaki; Ohtsuka Masayuki; Kato Atsushi; Yoshitomi Hideyuki; Furukawa Katsunori; Takayashiki Tsukasa; Miyazaki Masaru

来源：Journal of Hepato-Biliary-Pancreatic Sciences, 2016, 23(9): 574-584.

DOI：10.1002/jhbp.378

• 15-deoxy-delta12
• 14-prostaglandin J(2)
• Hepatocellular carcinoma
• Nuclear factor-B
• p27(kip1)
• Peroxisome proliferator-activated receptor-gamma

BackgroundThe prognosis of advanced hepatocellular carcinoma (HCC) is poor because of its rapid progression. Peroxisome proliferator-activated receptor-gamma (PPAR) is known to inhibit tumor growth in vitro; however, the behavior of PPAR in clinical cases of HCC remains uncertain.
MethodsSurgical specimens were collected from 104 HCC patients. The anti-neoplastic effects of PPAR were evaluated.
ResultsPPAR 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 expression. Moreover, low PPAR expression in HCC was an independent predictor of poorer prognosis. PPAR expression was positively correlated with PPAR activation and negatively correlated with NF-B activation in HCC. PPAR 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 ligands, PPAR activation was increased and cell proliferation was inhibited in a dose-dependent manner. In contrast, PPAR ligands negatively regulated NF-B activation.
ConclusionsActivation of PPAR induces cell cycle arrest and inhibits tumor progression by negatively regulating NF-B activation in HCC. Therefore, PPAR is an important endogenous regulator of HCC progression, and is a potential therapeutic target for HCC.

• 出版日期2016-9