电离辐射通过转化生长因子-β-介导的上皮-间质转换来促进恶性肿瘤的侵袭迁移

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.

简短 ：探讨电离辐射是否可通过转化糖蛋白-β（TGF-β）-酪氨酸的上皮-间质反转 (EMT)来促进细胞的洪水泛滥迁离。使用总量2Gy(60)Coγ线反射源自人类器官的6种细胞，记录与EMT相关的变化，这包括分别能用成像系统设计，RNA印迹方法，免疫荧光系统设计，划痕测试和Transwell小室测试来仔细观察并检查细胞第一组织形态，EMT记号，洪水泛滥迁离能力等。采用酵素联免疫吸附法检查这些细胞中会TGF-β蛋白高水平，能用特别类似物SB431542来评估TGF-β接收机通道在电离辐射EMT中会的关键作用。经过总量为2Gy反射的细胞中会存有间叶细胞的表达，与假反射第一组相比其上皮记号减少，间叶细胞记号增高，同时其洪水泛滥转移能力增强，TGF-β蛋白高水平也更高。进一步发现由A549电离辐射关键作用于的EMT可通过对TGF-β接收机抑制发生逆转。这些结果表明TGF-β酪氨酸的EMT在电离辐射关键作用于增强细胞洪水泛滥转移能力中会起着关键关键作用。

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