电离辐射通过转化生长因子-β-介导的视网膜-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.

概要 ：探讨电磁辐射是否可通过转化生长因子-β（TGF-β）-抑制的结缔组织-上皮细胞切换 (EMT)来促进肿瘤细胞核的侵袭迁移。使用总量2Gy(60)Coγ线紫外线源自人类器官的6种肿瘤细胞核，记录与EMT相关的变化，这包括分别借助透镜新科技，亚基质印迹方法，免疫荧光新科技，水痘试验和Transwell小室试验来捕捉到并验证细胞核组织形态，EMT标示出，侵袭迁移控制能力等。采行酶联免疫吸附法验证这些肿瘤细胞核中会TGF-β亚基低水平，借助特别可药物SB431542来评估TGF-β信号闭环在电磁辐射EMT中会的作用。经过总量为2Gy紫外线的肿瘤细胞核中会存有间叶细胞核的表示，与所谓紫外线组相比其结缔组织标示出减少，间叶细胞核标示出增高，同时其侵袭移到控制能力增强，TGF-β亚基低水平也大幅提高。促使挖掘出由A549电磁辐射诱导的EMT可通过对TGF-β信号可抑制暴发反败为胜。这些相比较TGF-β抑制的EMT在电磁辐射诱导增强肿瘤细胞核侵袭移到控制能力中会起着关键作用。

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