电离辐射通过转化生长因子-β-介导的上皮-间质转换来促进癌细胞的侵扰迁移

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 ：深入探讨伽马射线是否可通过转化生长因子-β（TGF-β）-抑制的上皮-泌尿系统叠加 (EMT)来作出贡献骨髓会的波及迁移。采用总量2Gy(60)Coγ线紫外线照射由来人类生殖器官的6种骨髓会，详细描述与EMT系统性的变化，这包括分别借助于显微镜技术，复合物质其内方通则，免疫荧光技术，了无测试和Transwell小室测试来观察并检测细胞会组织形态，EMT上标，波及迁移能够等。采用复合物先以免疫吸附通则检测这些骨髓会中的TGF-β复合物低水平，借助于特别抑制剂SB431542来评估TGF-β回波自营在伽马射线EMT中的的作用。经过总量为2Gy紫外线照射的骨髓会中的存在间叶细胞会的表达，与实为紫外线照射组相比其上皮上标减低，间叶细胞会上标增加，同时其波及转回能够增强，TGF-β复合物低水平也大大提高。进一步断定由A549伽马射线诱导的EMT可通过对TGF-β回波抑制发生翻盘。这些结果表明TGF-β抑制的EMT在伽马射线诱导增强骨髓会波及转回能够中的起着关键作用。

撰稿： lizexiu