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Int J Mol Sci. 2014 May 22;15(5):9160-72. doi: 10.3390/ijms15059160.

The peroxisome proliferator-activated receptor (PPAR) α agonist fenofibrate suppresses chemically induced lung alveolar proliferative lesions in male obese hyperlipidemic mice.

Author information

  • 1Department of Experimental Pathology and Tumor Biology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan. tkuno@med.nagoya-cu.ac.jp.
  • 2Department of Tumor Pathology, Graduate School of Medicine, Gifu University, Gifu 501-1194, Japan. k-hata-sun@hhc.eisai.co.jp.
  • 3Department of Tumor Pathology, Graduate School of Medicine, Gifu University, Gifu 501-1194, Japan. sw20.3s-gte@hotmail.co.jp.
  • 4Department of Tumor Pathology, Graduate School of Medicine, Gifu University, Gifu 501-1194, Japan. ahara@gifu-u.ac.jp.
  • 5Department of Pathology, Osaka Medical College, Osaka 569-8686, Japan. hirose@art.osaka-med.ac.jp.
  • 6Department of Experimental Pathology and Tumor Biology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan. sattak@med.nagoya-cu.ac.jp.
  • 7Onco-Pathology, Department of Pathology and Host-Defenses, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan. imaida@med.kagawa-u.ac.jp.
  • 8Department of Tumor Pathology, Graduate School of Medicine, Gifu University, Gifu 501-1194, Japan. takutt@toukaisaibou.co.jp.

Abstract

Activation of peroxisome proliferator-activated receptor (PPAR) α disrupts growth-related activities in a variety of human cancers. This study was designed to determine whether fenofibrate, a PPARα agonist, can suppress 4-nitroquinoline 1-oxide (4-NQO)-induced proliferative lesions in the lung of obese hyperlipidemic mice. Male Tsumura Suzuki Obese Diabetic mice were subcutaneously injected with 4-NQO to induce lung proliferative lesions, including adenocarcinomas. They were then fed a diet containing 0.01% or 0.05% fenofibrate for 29 weeks, starting 1 week after 4-NQO administration. At week 30, the incidence and multiplicity (number of lesions/mouse) of pulmonary proliferative lesions were lower in mice treated with 4-NQO and both doses of fenofibrate compared with those in mice treated with 4-NQO alone. The incidence and multiplicity of lesions were significantly lower in mice treated with 4-NQO and 0.05% fenofibrate compared with those in mice treated with 4-NQO alone (p<0.05). Both doses of fenofibrate significantly reduced the proliferative activity of the lesions in 4-NQO-treated mice (p<0.05). Fenofibrate also significantly reduced the serum insulin and insulin-like growth factor (IGF)-1 levels, and decreased the immunohistochemical expression of IGF-1 receptor (IGF-1R), phosphorylated Akt, and phosphorylated Erk1/2 in lung adenocarcinomas. Our results indicate that fenofibrate can prevent the development of 4-NQO-induced proliferative lesions in the lung by modulating the insulin-IGF axis.

PMID:
24857924
[PubMed - indexed for MEDLINE]
PMCID:
PMC4057781
Free PMC Article
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