电离辐射通过转化生长因子-β-介导的结缔组织-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 ：探讨电离辐射究竟可通过转化激酵素-β（TGF-β）-抑制的黏膜-间质转化 (EMT)来促进恶性肿瘤的首当其冲搬迁。应用于总量2Gy(60)Coγ支线照射来源于人类器官的6种恶性肿瘤，记录与EMT系统性的改变，这之外分别为了让镜片关键技术，肽质印迹方法，免疫荧光关键技术，凹凸试验和Transwell小室试验来观察并检测细胞小组织形态，EMT标有，首当其冲搬迁意志力等。使用酵素联免疫吸附法检测这些恶性肿瘤里TGF-β肽水平，为了让特别酶抑制剂SB431542来审核TGF-β瞬时通路在电离辐射EMT里的抑制作用。经过总量为2Gy照射的恶性肿瘤里存在间叶细胞的暗示，与实为照射小组相比其黏膜标有减少，间叶细胞标有缩减，同时其首当其冲转移意志力减慢，TGF-β肽水平也提高。进一步发现由A549电离辐射抑止的EMT可通过对TGF-β瞬时抑制牵涉到再一。这些结果表明TGF-β抑制的EMT在电离辐射抑止减慢恶性肿瘤首当其冲转移意志力里起着关键抑制作用。

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