电离辐射通过转化生长因子-β-介导的上皮-间质转换来倡导癌细胞的侵袭迁移

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 ：概述放射确实可通过转化生长因子-β（TGF-β）-依赖性的上皮-间质转换 (EMT)来促进恶性肿瘤的来袭迁移。使用工业产值2Gy(60)Coγ本站反射源自人类心脏的6种恶性肿瘤，纪录与EMT就其的改变，这有数分别利用电子显微镜电子技术，核酸印迹工具，免疫荧光电子技术，划痕试验性和Transwell小室试验性来观察并样品细胞膜组织形态，EMT标上，来袭迁移意志力等。运用于酶联免疫吸附法样品这些恶性肿瘤之前TGF-β复合物低水平，利用特别抑制剂SB431542来评估TGF-β信号通路在放射EMT之前的效用。经过工业产值为2Gy反射的恶性肿瘤之前普遍存在间叶细胞膜的理解，与所谓反射组相比其上皮标上减少，间叶细胞膜标上增加，同时其来袭转移意志力大幅提高，TGF-β复合物低水平也提高。促使发现由A549放射诱导的EMT可通过对TGF-β信号抑制暴发逆转。这些结果表明TGF-β依赖性的EMT在放射诱导大幅提高恶性肿瘤来袭转移意志力之前起着关键效用。

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