电离辐射通过转化生长因子-β-介导的上皮-间质转换来促进免疫系统的侵袭迁移

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 ：深入探讨电离辐射是否可通过转变成激酶-β（TGF-β）-抑制的上皮-间质变换 (EMT)来有助于肝细胞的侵入迁移。使用总和2Gy(60)Coγ支线照射源自生命循环系统的6种肝细胞，记录与EMT相关的变化，这包括分别利用显微镜技术，抗原斯塔夫基方法，免疫荧光技术，划痕试验性和Transwell小室试验性来捕捉到并检测细胞组织形态，EMT上标，侵入迁移并能等。转用酶亦同免疫吸附法检测这些肝细胞当中TGF-β抗原程度，利用特别选择性SB431542来评估TGF-β讯号通路在电离辐射EMT当中的作用。经过总和为2Gy照射的肝细胞当中存在间叶细胞的表达，与所谓照射组远比其上皮上标增大，间叶细胞上标增加，同时其侵入移出并能进一步降低，TGF-β抗原程度也降低。进一步发现由A549电离辐射正向的EMT可通过对TGF-β讯号选择性发生逆转。这些结果表明TGF-β抑制的EMT在电离辐射正向进一步降低肝细胞侵入移出并能当中起着关键作用。

主笔： lizexiu