Activation of peroxisome proliferator‐activated receptor‐gamma inhibits tumor growth by negatively regulating nuclear factor‐κB activation in patients with hepatocellular carcinoma. (16th August 2016)

• Record Type: Journal Article
• Authors: Nojima, Hiroyuki; Kuboki, Satoshi; Shinoda, Kimio; Shimizu, Hiroaki; Ohtsuka, Masayuki; Kato, Atsushi; Yoshitomi, Hideyuki; Furukawa, Katsunori; Takayashiki, Tsukasa; Miyazaki, Masaru
• Is Part Of: Journal of hepato-biliary-pancreatic sciences. Volume 23:Number 9(2016)
• Page Start: 574
• Page End: 584
• Publication Date: 2016-08-16
• Subjects: 15‐deoxy‐delta12, 14‐prostaglandin J2 -- Hepatocellular carcinoma -- Nuclear factor‐κB -- p27(kip1) -- Peroxisome proliferator‐activated receptor‐gamma; Liver -- Diseases -- Periodicals; Biliary tract -- Diseases -- Periodicals; Pancreas -- Diseases -- Periodicals; 617.556
• DOI: 10.1002/jhbp.378
• Languages: English
• ISSNs: 1868-6974

Abstract

Abstract: Background: The prognosis of advanced hepatocellular carcinoma (HCC) is poor because of its rapid progression. Peroxisome proliferator‐activated receptor‐gamma (PPARγ) is known to inhibit tumor growth in vitro ; however, the behavior of PPARγ in clinical cases of HCC remains uncertain. Methods: Surgical specimens were collected from 104 HCC patients. The anti‐neoplastic effects of PPARγ were evaluated. Results: PPARγ 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 PPARγ expression. Moreover, low PPARγ expression in HCC was an independent predictor of poorer prognosis. PPARγ expression was positively correlated with PPARγ activation and negatively correlated with NF‐κB activation in HCC. PPARγ 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 PPARγ ligands, PPARγ activation was increased and cell proliferation was inhibited in a dose‐dependent manner. In contrast, PPARγ ligands negatively regulated NF‐κB activation. Conclusions: Activation of PPARγ induces cell cycle arrest and inhibits tumor progression by negatively regulating NF‐κB activation in HCC. Therefore, PPARγ is an important endogenous regulator of HCC progression, and is a potential therapeutic target for HCC. Abstract : Highlight Nojima and colleagues set out to elucidate the behavior of PPARγ, which is known to inhibit tumor growth in vitro, in clinical cases of hepatocellular carcinoma. Increased PPARγ ligands enhanced the expression and activation of PPARγ, showing anti‐neoplastic effects by inducing cell cycle arrest through the inhibition of NF‐γB activation.