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）-介导的腺体-脂质匹配 (EMT)来加强癌线粒体的侵袭移至。使用总量2Gy(60)Coγ线反射是从生物器官的6种癌线粒体，记录与EMT相关的变化，这包括分别借助于孔径电子技术，蛋白质质印迹步骤，免疫荧光电子技术，了无实验和Transwell泽田实验来掩蔽并检验线粒体组织形态，EMT标示出，侵袭移至控制能力等。采用酶及第免疫吸附法则检验这些癌线粒体中所TGF-β蛋白质水平，借助于之外诱发剂SB431542来评估TGF-β瞬时移动式在电离辐射EMT中所的作用。经过总量为2Gy反射的癌线粒体中所存在间叶线粒体的表达，与假反射组相比较其腺体标示出提高，间叶线粒体标示出减低，同时其侵袭重新分配控制能力减慢，TGF-β蛋白质水平也提高。全面发现由A549电离辐射诱导的EMT可通过对TGF-β瞬时诱发发生逆转。这些结果表明TGF-β介导的EMT在电离辐射诱导减慢癌线粒体侵袭重新分配控制能力中所起着关键作用。

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