电离辐射通过转化生长因子-β-介导的上皮-间质转换来推动癌细胞的侵袭迁移

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 ：探讨电离辐射是否可通过转化生长因子-β（TGF-β）-介导的内膜-内膜转换 (EMT)来作出贡献肿瘤核的蹂躏迁移。使用工业产值2Gy(60)Coγ线太阳光源自人类肝脏的6种肿瘤核，日志与EMT相关的变化，这包括分别利用显微镜电子技术，RNA印迹方法，免疫荧光电子技术，划痕试验车和Transwell的大试验车来检视并检测细胞核组织有机体，EMT标上，蹂躏迁移能够等。采用酶联成免疫吸附法检测这些肿瘤核之中TGF-β蛋白水平，利用同样选择性剂SB431542来评估TGF-β信号通路在电离辐射EMT之中的作用。经过工业产值为2Gy太阳光的肿瘤核之中存在间叶细胞核的表达，与假太阳光组相比其内膜标上减低，间叶细胞核标上减小，同时其蹂躏重新分配能够加强，TGF-β蛋白水平也提高。进一步发现由A549电离辐射作用于的EMT可通过对TGF-β信号选择性发生逆转。这些结果表明TGF-β介导的EMT在电离辐射作用于加强肿瘤核蹂躏重新分配能够之中起着关键作用。

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