电离辐射通过转化生长因子-β-介导的腺体-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 ：探讨紫外线是否可通过转化趋化因子-β（TGF-β）-介导的上皮-间质转成 (EMT)来增进癌蛋白质的摧残迁到。适用总量2Gy(60)Coγ线强光源自全人类器官的6种癌蛋白质，记录与EMT系统性的变化，这包括分别借助显微镜技术，蛋白质内质其内方例，免疫荧光技术，了无试验和Transwell小室试验来观察并检测蛋白质组织有机体，EMT标上，摧残迁到能力等。采用复合物联免疫吸附例检测这些癌蛋白质里TGF-β蛋白质内水平，借助特别类固醇SB431542来审计TGF-β波形通路在紫外线EMT里的发挥作用。经过总量为2Gy强光的癌蛋白质里存在间叶蛋白质的表达，与假强光组远比其上皮标上减少，间叶蛋白质标上增加，同时其摧残移出能力增强，TGF-β蛋白质内水平也提高。必要性发现由A549紫外线诱导的EMT可通过对TGF-β波形抑制发生逆转。这些结果表明TGF-β介导的EMT在紫外线诱导增强癌蛋白质摧残移出能力里起着关键发挥作用。

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