title: Activation of peroxisome proliferator-activated receptor-gamma inhibits tumor growth by negatively regulating nuclear factor-κB activation in patients with hepatocellular carcinoma.
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.
authors.affiliation: Department of General Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-0856, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nojima
authors.affiliation: Department of General Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-0856, Japan. satoshi.kuboki@faculty.chiba-u.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kuboki
authors.affiliation: Department of General Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-0856, Japan.
authors.forename: Kimio
authors.initials: K
authors.lastname: Shinoda
authors.affiliation: Department of General Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-0856, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimizu
authors.affiliation: Department of General Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-0856, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ohtsuka
authors.affiliation: Department of General Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-0856, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kato
authors.affiliation: Department of General Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-0856, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yoshitomi
authors.affiliation: Department of General Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-0856, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Furukawa
authors.affiliation: Department of General Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-0856, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Takayashiki
authors.affiliation: Department of General Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-0856, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Miyazaki
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D049109:Cell Proliferation; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007564:Japan; D008113:Liver Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism*; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D046509:Tissue Culture Techniques; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D016328:NF-kappa B; D047495:PPAR gamma
keywords: 15-deoxy-delta12,14-prostaglandin J2; Hepatocellular carcinoma; Nuclear factor-κB; Peroxisome proliferator-activated receptor-gamma; p27(kip1)