The Peroxisome Proliferator-Activated Receptor (PPAR) α Agonist Fenofibrate Suppresses Chemically Induced Lung Alveolar Proliferative Lesions in Male Obese Hyperlipidemic Mice

International Journal of Molecular Sciences

Toshiya Kuno³  Kazuya Hata⁴  Manabu Takamatsu⁴  Akira Hara⁴  Yoshinobu Hirose¹  Satoru Takahashi³  Katsumi Imaida² 

[1] Department of Pathology, Osaka Medical College, Osaka 569-8686, Japan; E-Mail:;Onco-Pathology, Department of Pathology and Host-Defenses, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan; E-Mail:;Department of Experimental Pathology and Tumor Biology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan; E-Mail:;Department of Tumor Pathology, Graduate School of Medicine, Gifu University, Gifu 501-1194, Japan; E-Mails:

关键词: 4-nitroquinoline-1-oxide;    lung neoplasms;    carcinogenesis;    hyperlipidemia;    hyperinsulinemia;    chemoprevention;   

DOI  :  10.3390/ijms15059160

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland