电离辐射通过转化生长因子-β-介导的上皮-脂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 ：探讨辐射源确实可通过转换成激酶-β（TGF-β）-抑制的上皮-游离转换 (EMT)来促进肝巨噬细胞的肆虐迁到。适用增幅2Gy(60)Coγ线紫外线照射源自人类器官的6种肝巨噬细胞，历史纪录与EMT具体的变化，这包含分别利用电子显微镜核心技术，蛋白印迹方式，免疫荧光核心技术，污渍测试和Transwell小室测试来观察并样品巨噬细胞分组织结构上，EMT标明，肆虐迁到能力等。有别于酶联免疫吸附法样品这些肝巨噬细胞中的TGF-β蛋白水平，利用特别衍生物SB431542来评估TGF-β接收器通路在辐射源EMT中的的作用。经过增幅为2Gy紫外线照射的肝巨噬细胞中的发挥作用间叶巨噬细胞的表达，与骗紫外线照射分组相比其上皮标明减少，间叶巨噬细胞标明减低，同时其肆虐转移能力减慢，TGF-β蛋白水平也提高。进一步推断出由A549辐射源诱导的EMT可通过对TGF-β接收器诱发发生反转。这些试验中TGF-β抑制的EMT在辐射源诱导减慢肝巨噬细胞肆虐转移能力中的起着关键作用。

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