电离辐射通过转化生长因子-β-介导的上皮细胞-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.

简述 ：探讨放射是否可通过转化生长因子-β（TGF-β）-诱导的结缔组织-间质转换 (EMT)来促进恶性肿瘤的洪水泛滥迁离。用作总量2Gy(60)Coγ线强光意指人类文明器官的6种恶性肿瘤，记录与EMT涉及的变化，这之外分别利用显微镜应用，蛋白质印迹方法，免疫荧光应用，划痕试验和Transwell小室试验来仔细观察并检测细胞组织特征，EMT标识，洪水泛滥迁离控制能力等。运用于蛋白先以免疫吸附法检测这些恶性肿瘤之前TGF-β蛋白水平，利用引人注意抑制剂SB431542来审计TGF-β波形通路在放射EMT之前的作用。经过总量为2Gy强光的恶性肿瘤之前存在间叶细胞的理解，与骗强光组来得其结缔组织标识减少，间叶细胞标识增加，同时其洪水泛滥转移控制能力提升，TGF-β蛋白水平也提高。进一步发现由A549放射诱导的EMT可通过对TGF-β波形抑制引发关键时刻。这些分析表明TGF-β诱导的EMT在放射诱导提升恶性肿瘤洪水泛滥转移控制能力之前起着关键人物。

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