电离辐射通过转化生长因子-β-介导的上皮-间质转换来促进癌细胞的洪水泛滥迁移

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 ：阐释宇宙射线是否可通过转化糖蛋白-β（TGF-β）-诱导的上皮线粒体-间质转换 (EMT)来促进肿瘤的侵袭迁移。使用总量2Gy(60)Coγ终点站照射起源于人类器官的6种肿瘤，记录与EMT相关的改变，这仅限于分别并用显微镜高效率，线粒体内其内方法，免疫荧光高效率，划痕试验中和Transwell小室试验中来仔细观察并检验线粒体组织共通点，EMT上标，侵袭迁移能力也等。采用底物联成免疫吸附法检验这些肿瘤中会TGF-β蛋白质水准，并用同样抑制剂SB431542来评量TGF-β接收器路中在宇宙射线EMT中会的效用。经过总量为2Gy照射的肿瘤中会共存间叶线粒体的暗示，与有假照射组相比之下其上皮线粒体上标减低，间叶线粒体上标减低，同时其侵袭转移能力也增强，TGF-β蛋白质水准也减低。进一步辨认出由A549宇宙射线抑制的EMT可通过对TGF-β接收器抑制暴发逆转。这些结果表明TGF-β诱导的EMT在宇宙射线抑制增强肿瘤侵袭转移能力也中会起着关键效用。

总编： lizexiu