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
Abstract
To 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）-介导的上皮-间质转换 (EMT)来促进癌细胞的侵袭迁移。使用总量2Gy(60)Coγ线照射源自人类器官的6种癌细胞，记录与EMT相关的变化，这包括分别利用显微镜技术，蛋白质印迹方法，免疫荧光技术，划痕试验和Transwell小室试验来观察并检测细胞组织形态，EMT标记，侵袭迁移能力等。采用酶联免疫吸附法检测这些癌细胞中TGF-β蛋白水平，利用特别抑制剂SB431542来评估TGF-β信号通路在电离辐射EMT中的作用。经过总量为2Gy照射的癌细胞中存在间叶细胞的表达，与假照射组相比其上皮标记减少，间叶细胞标记增加，同时其侵袭转移能力增强，TGF-β蛋白水平也提高。进一步发现由A549电离辐射诱导的EMT可通过对TGF-β信号抑制发生逆转。这些结果表明TGF-β介导的EMT在电离辐射诱导增强癌细胞侵袭转移能力中起着关键作用。
