电离辐射通过转化生长因子-β-介导的上皮-间质转换来促使癌细胞的侵袭迁移

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 ：探讨宇宙射线前提可通过转成生长因子-β（TGF-β）-内皮细胞的结缔组织-间质转换 (EMT)来有利于肿瘤细胞的侵袭移入。应用于分之一2Gy(60)Coγ直通照射源自进化心脏的6种肿瘤细胞，记录与EMT相关的改变，这包括分别利用显微镜技术开发，复合物质印迹方法，免疫荧光技术开发，划痕试验和Transwell小室试验来观察并检测细胞一组织形态，EMT标上，侵袭移入能力等。采用酵素同德免疫吸附法检测这些肿瘤细胞之前TGF-β复合物水平，利用同样诱发剂SB431542来分析TGF-β信号通路在宇宙射线EMT之前的发挥作用。经过分之一为2Gy照射的肿瘤细胞之前长期存在间叶细胞的表达，与所谓照射一组相比其结缔组织标上减少，间叶细胞标上降低，同时其侵袭移转到能力增强，TGF-β复合物水平也提高。进一步发现由A549宇宙射线诱导的EMT可通过对TGF-β信号诱发发生逆转。这些结果表明TGF-β内皮细胞的EMT在宇宙射线诱导增强肿瘤细胞侵袭移转到能力之前起着关键发挥作用。

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