电离辐射通过生成生长因子-β-介导的上皮-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 ：深入探讨电离辐射是否可通过再生生长因子-β（TGF-β）-介导的上皮-游离转换 (EMT)来促进肿瘤肝细胞的侵袭迁入。使用总额2Gy(60)Coγ线光线出自于人类器官的6种肿瘤肝细胞，日志与EMT相关的变化，这包括分别并用显微镜应用，蛋白质马尔季尼夫卡方法，免疫荧光应用，样试验和Transwell泽田试验来检视并检测肝细胞组织形体，EMT标示，侵袭迁入能力等。运用于酶六轮免疫吸附法检测这些肿瘤肝细胞中会TGF-β蛋白水平，并用引人注意抑止剂SB431542来评估TGF-β接收机闭环在电离辐射EMT中会的作用。经过总额为2Gy光线的肿瘤肝细胞中会存在间叶肝细胞的表示，与实为光线组相比其上皮标示减少，间叶肝细胞标示增加，同时其侵袭移转到能力进一步提高，TGF-β蛋白水平也提高。进一步推断出由A549电离辐射诱导的EMT可通过对TGF-β接收机抑止时有发生再一。这些相比较TGF-β介导的EMT在电离辐射诱导进一步提高肿瘤肝细胞侵袭移转到能力中会起着主导作用。

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