电离辐射通过转化生长因子-β-介导的上皮-间质转换来促使癌细胞的侵袭迁移

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 ：反思辐射源是否是可通过转化生长因子-β（TGF-β）-介导的表皮-间质转换 (EMT)来促进癌线或粒体的侵袭迁移。使用总量2Gy(60)Coγ线或光照源自人类器官的6种癌线或粒体，记录与EMT无关的发生变化，这包括分别利用透镜电子技术，亚基质印迹方法，免疫荧光电子技术，水痘次测试和Transwell小室次测试来观察并检测线或粒体组织构造，EMT标记，侵袭迁移控制能力等。采用酶联免疫吸附法检测这些癌线或粒体中会TGF-β亚基素质，利用特别抑制剂SB431542来审计TGF-β接收器通路在辐射源EMT中会的作用。经过总量为2Gy光照的癌线或粒体中会不存在间叶线或粒体的表达，与假光照组相比其表皮标记减少，间叶线或粒体标记增加，同时其侵袭转回控制能力增强，TGF-β亚基素质也减低。进一步发现由A549辐射源诱导的EMT可通过对TGF-β接收器抑制发生逆转。这些结果表明TGF-β介导的EMT在辐射源诱导增强癌线或粒体侵袭转回控制能力中会起着巨大作用。

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