电离辐射通过转化细胞因子-β-介导的上皮-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 ：探讨电离辐射是否可通过转化生长因子-β（TGF-β）-诱导的上皮-粘液转换 (EMT)来有助于癌巨噬细胞的首当其冲迁移。使用年均2Gy(60)Coγ新线光新线源自人类肝脏的6种癌巨噬细胞，记录与EMT相关的变化，这有数分别利用显微镜关键技术，细胞内；还有方国法，免疫荧光关键技术，划痕试验和Transwell小室试验来通过观察并监测巨噬细胞组织形态，EMT上标，首当其冲迁移战斗能力等。采用激酶联免疫吸附国法监测这些癌巨噬细胞中都TGF-β细胞内水平，利用特别肽SB431542来评估TGF-β路径通路在电离辐射EMT中都的依赖性。经过年均为2Gy光新线的癌巨噬细胞中都存在间叶巨噬细胞的强调，与假光新线组相比其上皮上标减少，间叶巨噬细胞上标提高，同时其首当其冲重新分配战斗能力减弱，TGF-β细胞内水平也提高。进一步发现由A549电离辐射可借的EMT可通过对TGF-β路径依赖性发生逆转。这些结果表明TGF-β诱导的EMT在电离辐射可借减弱癌巨噬细胞首当其冲重新分配战斗能力中都起着起着。

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