电离辐射通过转化生长因子-β-介导的表皮-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 ：探讨宇宙射线是否可通过转化成生长因子-β（TGF-β）-介导的内膜-粘液转换 (EMT)来促进恶性肿瘤的肆虐迁离。使用分之一2Gy(60)Coγ线照射源自全人类器官的6种恶性肿瘤，记录与EMT相关的转变，这包括分别利用显微镜系统设计，复合物质印迹方国法，免疫荧光系统设计，样试验和Transwell小室试验来观察并样品细胞组织形态，EMT标记，肆虐迁离意志力等。采用酶嗣后免疫吸附国法样品这些恶性肿瘤之中TGF-β复合物水平，利用引人注意类固醇SB431542来评估TGF-β信号通路在宇宙射线EMT之中的功用。经过分之一为2Gy照射的恶性肿瘤之中长期存在间叶细胞的表达，与假照射组相比其内膜标记减少，间叶细胞标记增加，同时其肆虐转移意志力增强，TGF-β复合物水平也降低。进一步发现由A549宇宙射线功用于的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在宇宙射线功用于增强恶性肿瘤肆虐转移意志力之中起着关键人物。

校对： lizexiu