电离辐射通过转化生长因子-β-介导的上皮-脂质转换来促进癌细胞的侵袭迁移

Int J Radiat Oncol Biol Phys 2011 Dec;81 (5): 1530-7. [IF:4.503]Ionizing radiation promotes migration and invasion of cancer cells through transforming growth factor-Beta-mediated epithelial-mesenchymal transition.Zhou YC , Liu JY , Li J , Zhang J , Xu YQ , Zhang HW , Qiu LB , Ding GR , Su XM , Mei-Shi , Guo GZ .Department of Radiation Oncology, Xijing Hospital Fourth Military Medical University, Xi'an, China; Department of Radiation Medicine, College of Preventive Medicine, Xijing Hospital Fourth Military Medical University, Xi'an, China.第四军医大学西京医院放射科

AbstractTo examine whether ionizing radiation enhances the migratory and invasive abilities of cancer cells through transforming growth factor (TGF-β)-mediated epithelial-mesenchymal transition (EMT). Six cancer cell lines originating from different human organs were irradiated by (60)Co γ-ray at a total dose of 2 Gy, and the changes associated with EMT, including morphology, EMT markers, migration and invasion, were observed by microscope, Western blot, immunofluorescence, scratch assay, and transwell chamber assay, respectively. Then the protein levels of TGF-β in these cancer cells were detected by enzyme-linked immunosorbent assay, and the role of TGF-β signaling pathway in the effect of ionizing radiation on EMT was investigate by using the specific inhibitor SB431542. After irradiation with γ-ray at a total dose of 2 Gy, cancer cells presented the mesenchymal phenotype, and compared with the sham-irradiation group the expression of epithelial markers was decreased and of mesenchymal markers was increased, the migratory and invasive capabilities were strengthened, and the protein levels of TGF-β were enhanced. Furthermore, events associated with EMT induced by IR in A549 could be reversed through inhibition of TGF-β signaling. These results suggest that EMT mediated by TGF-β plays a critical role in IR-induced enhancing of migratory and invasive capabilities in cancer cells.

摘要 ：探讨电离辐射到底可通过转化生长因子-β（TGF-β）-介导的黏膜-间质转换 (EMT)来促进免疫肝细胞的侵袭迁往。使用存量2Gy(60)Coγ线紫外线照射源自人类肾脏的6种免疫肝细胞，记录与EMT相关的变化，这包括分别依靠显微镜技术开发，酵素印迹方国法，免疫荧光技术开发，划痕次测试和Transwell泽田次测试来捕捉到并样品肝细胞组织特征，EMT记号，侵袭迁往控制能力等。选用酶六轮免疫吸附国法样品这些免疫肝细胞中TGF-β蛋白水平，依靠特别肽SB431542来分析报告TGF-β接收器通路在电离辐射EMT中的作用。经过存量为2Gy紫外线照射的免疫肝细胞中普遍存在间叶肝细胞的表达，与真紫外线照射组相比其黏膜记号提高，间叶肝细胞记号增大，同时其侵袭转移控制能力弱化，TGF-β蛋白水平也降低。再进一步发现由A549电离辐射诱发的EMT可通过对TGF-β接收器依赖性发生翻盘。这些结果显示TGF-β介导的EMT在电离辐射诱发弱化免疫肝细胞侵袭转移控制能力中起着关键作用。

校对： lizexiu