Attenuation of metformin on radiation-induced lung fibrosis in rats
10.3760/cma.j.issn.0254-5098.2017.10.003
- VernacularTitle:二甲双胍对大鼠放射性肺纤维化的防治作用机制
- Author:
Ye WANG
1
;
Yongchao XIONG
;
Shaobo XUE
;
Zhihua WU
;
Zhenjun PENG
Author Information
1. 华中科技大学同济医学院附属协和医院肿瘤中心
- Keywords:
Metformin;
Radiation-induced pulmonary injury;
Transforming growth factor-β;
Fibrosis
- From:
Chinese Journal of Radiological Medicine and Protection
2017;37(10):736-741
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the radioprotective effects of metformin on radiation-induced pulmonary injury in rats. Method A total of 30 Sprague-Dawley ( SD) rats were randomly divided into three groups:control, radiation (20 Gy) and radiation (20 Gy) with metformin, with 10 rats in each group. The right lungs of rats were irradiated to 20 Gy with 6 MV X-rays. Computed tomography (CT) was performed and Hounsfield Units ( HU) were determined during the observation period. The tissue samples of lung were extracted to perform the histological analysis, measurement of hydroxyproline content, fibrosis score and evaluation of fibrosis/inflammatory markers by Western blot at 12 weeks post-irradiation. CCK-8 method was used to explore the effects of metformin on non-small cell lung cancer( NSCLC) cells A549 and H460. Results Metformin reduced radiologic and histologic signs of fibrosis, lung density(6. 52 ± 0. 43 vs. 3. 31 ± 0. 57, t=6. 37, P<0. 01) and hydroxyproline content(32. 58 ± 1. 59 vs. 23. 47 ± 2. 46,t=12. 72, P<0. 01) which had been increased due to irradiation. Meanwhile, it significantly decreased the expressions of Col1, p-AMPKα and TGF-β, while inhibited the expressions of p-Smad2 and p-Smad3 compared to the irradiation alone group. Moreover, metformin reduced A549 and H460 cells growth. Conclusions Metformin exerted a protective effect on normal tissues in radiation-induced pulmonary fibrosis. Thus, it might act as a promising radioprotective agent in the treatment of lung cancer.
