电离辐射通过转变成生长因子-β-介导的上皮-间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 ：探讨辐射源是否可通过转化激酶-β（TGF-β）-内皮细胞的上皮-间质转换 (EMT)来促进免疫细胞内的侵入搬迁。使用增幅2Gy(60)Coγ线强光源自生命体器官的6种免疫细胞内，纪录与EMT相关的波动，这包括分别依靠显微镜关键技术，肽质印迹方法，免疫荧光关键技术，划痕试验性和Transwell张以试验性来观察并验证细胞内组织形态，EMT上面，侵入搬迁能够等。采用酶联免疫吸附法验证这些免疫细胞内中TGF-β肽高度，依靠特别抑制剂SB431542来评估TGF-β信号通路在辐射源EMT中的起着。经过增幅为2Gy强光的免疫细胞内中不存在间叶细胞内的表达，与假强光组相比其上皮上面减少，间叶细胞内上面减少，同时其侵入转移能够强化，TGF-β肽高度也更高。进一步挖掘出由A549辐射源可借的EMT可通过对TGF-β信号抑制发生制胜。这些相比较TGF-β内皮细胞的EMT在辐射源可借强化免疫细胞内侵入转移能够中起着关键起着。

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