电离辐射通过转化生长因子-β-介导的结缔组织-间质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 ：探讨辐射源是否可通过转化生长因子-β（TGF-β）-介导的内膜-间质转成 (EMT)来促进免疫细胞膜的首当其冲迁往。应用于增幅2Gy(60)Coγ线强光源自人类器官的6种免疫细胞膜，记录与EMT相关的变化，这之外分别为了让显微镜系统设计，蛋白质索科利夫卡方法有，免疫荧光系统设计，划痕实验和Transwell小室实验来捕捉到并侦测细胞膜组织基本上，EMT标示，首当其冲迁往能力也等。选用酶联免疫吸附法侦测这些免疫细胞膜之前TGF-β蛋白高水平，为了让特别抑制剂SB431542来评估TGF-β路径通路在辐射源EMT之前的作用。经过增幅为2Gy强光的免疫细胞膜之前存在间叶细胞膜的表达，与实为强光组相比其内膜标示减小，间叶细胞膜标示增加，同时其首当其冲转移能力也强化，TGF-β蛋白高水平也减小。进一步发现由A549辐射源诱导的EMT可通过对TGF-β路径抑制发生大逆转。这些结果表明TGF-β介导的EMT在辐射源诱导强化免疫细胞膜首当其冲转移能力也之前起着巨大作用。

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