Changes in abilities of invasion and metastasis in surviving human lung adenocarcinoma (A549) cells after X-ray irradiation and related mechanism / 中华放射肿瘤学杂志

ABSTRACT

Objective To investigate the changes in the abilities of invasion and metastasis in surviving human lung adenocarcinoma (A549) cells after X-ray irradiation and the related mechanism.Methods The change in radiosensitivity after X-ray irradiation was determined by colony formation assay.The abilities of invasion and metastasis were evaluated by MTF adhesion assay and Transwell invasion and migration assay in vitro.The mRNA and protein expression of E-cadherin,vimentin,tumor growth factor (TGF)-β1,matrix metalloproteinase (MMP)-2,and MMP-9 was measured by real-time RT-PCR using SYBR Green fluorescence and Western blot.Results The colony formation assay showed that the surviving A549 cells after X-ray irradiation were more resistant to irradiation (ratio of D0 values =0.94).Their abilities of adhesion,invasion,and migration were significantly increased by 1.46 times,1.40 times,and 1.45 times,respectively.In addition,the surviving cells showed enlarged intercellular spaces and had many long pseudopodi.Compared with those in the control group,the mRNA expression levels of vimentin,TGF-β1,MMP-2,and MMP-9 of surviving cells were increased by 1.37 times,2.37 times,1.80 times,and 1.50 times,respectively,the protein expression levels of the above substances were increased by 1.60 times,1.80 times,1.10 times,and 1.20 times,respectively,and the mRNA and protein expression levels of E-cadherin were decreased by 59.4％ and 74.6％.Conclusions The surviving A549 cells after X-ray irradiation have significantly increased abilities of invasion and metastasis.This may be due to radiationinduced TGF-β1 expression increase that in turn promotes epithelial-mesenchymal transition and also due to radiation-induced MMP-2 and MMP-9 expression increase.