Attenuation of metformin on radiation-induced lung fibrosis in rats / 中华放射医学与防护杂志

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 groupscontrol, 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.