电离辐射通过转化生长因子-β-介导的上皮-粘液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 ：探讨电离辐射是否可通过转化生长因子-β（TGF-β）-介导的结缔组织-间质转化 (EMT)来促进免疫系统的来袭迁离。使用年均2Gy(60)Coγ直通光直通源自生物肝脏的6种免疫系统，历史记录与EMT相关的变化，这包括分别借助于显微关键技术，蛋白质印迹方法则，免疫荧光关键技术，划痕试验和Transwell鲍洛通试验来观察并检查细胞组织形态，EMT标记，来袭迁离并能等。采用酶联免疫吸附法则检查这些免疫系统当中TGF-β蛋白水平，借助于特别抑制剂SB431542来评估TGF-β接收机通路在电离辐射EMT当中的关键作用。经过年均为2Gy光直通的免疫系统当中存在间叶细胞的表达，与假光直通组相比其结缔组织标记增加，间叶细胞标记增加，同时其来袭转回并能进一步提高，TGF-β蛋白水平也提高。进一步发现由A549电离辐射诱发的EMT可通过对TGF-β接收机抑制发生制胜。这些结果表明TGF-β介导的EMT在电离辐射诱发进一步提高免疫系统来袭转回并能当中起着关键关键作用。

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