Next Article in Journal
Expression of Human Endogenous Retrovirus env Genes in the Blood of Breast Cancer Patients
Previous Article in Journal
Functional Polymorphisms of the ABCG2 Gene Are Associated with Gout Disease in the Chinese Han Male Population
Article Menu

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2014, 15(5), 9160-9172; 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

1
Department of Experimental Pathology and Tumor Biology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan
2
Department of Tumor Pathology, Graduate School of Medicine, Gifu University, Gifu 501-1194, Japan
3
Department of Pathology, Osaka Medical College, Osaka 569-8686, Japan
4
Onco-Pathology, Department of Pathology and Host-Defenses, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan
5
Department of Diagnostic Pathology & Research Center of Diagnostic Pathology, Gifu Municipal Hospital, Gifu 500-8513, Japan
*
Author to whom correspondence should be addressed.
Received: 6 March 2014 / Revised: 7 May 2014 / Accepted: 12 May 2014 / Published: 22 May 2014
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
View Full-Text   |   Download PDF [2622 KB, uploaded 19 June 2014]   |  

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. View Full-Text
Keywords: 4-nitroquinoline-1-oxide; lung neoplasms; carcinogenesis; hyperlipidemia; hyperinsulinemia; chemoprevention 4-nitroquinoline-1-oxide; lung neoplasms; carcinogenesis; hyperlipidemia; hyperinsulinemia; chemoprevention
Figures

This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Kuno, T.; Hata, K.; Takamatsu, M.; Hara, A.; Hirose, Y.; Takahashi, S.; Imaida, K.; Tanaka, T. The Peroxisome Proliferator-Activated Receptor (PPAR) α Agonist Fenofibrate Suppresses Chemically Induced Lung Alveolar Proliferative Lesions in Male Obese Hyperlipidemic Mice. Int. J. Mol. Sci. 2014, 15, 9160-9172.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top