IONIZING RADIATION PROMOTES MIGRATION AND INVASION OF CANCER CELLS THROUGH TRANSFORMING GROWTH FACTOR-BETA-MEDIATED EPITHELIAL MESENCHYMAL TRANSITION
IONIZING RADIATION PROMOTES MIGRATION AND INVASION OF CANCER CELLS THROUGH TRANSFORMING GROWTH FACTOR-BETA-MEDIATED EPITHELIAL MESENCHYMAL TRANSITION
复制标题
电离辐射通过转化生长因子-β介导的上皮间质转化促进癌细胞的迁移和侵袭
DOI：
10.1016/j.ijrobp.2011.06.1956
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发表时间：
2011-12-01
影响因子：
7
通讯作者：
Guo, Guo-Zhen
中科院分区：
文献类型：
--
作者：
Zhou, Yong-Chun;Liu, Jun-Ye;Guo, Guo-Zhen
目的：探讨电离辐射是否通过转化生长因子（tgf - β）介导的上皮-间质转化（EMT）增强癌细胞的迁移和侵袭能力。方法与材料：采用总剂量为2 Gy的Co-60 γ射线照射人体不同器官的6株癌细胞，分别采用显微镜、Western blot、免疫荧光、划痕法、transwell室法观察EMT相关的形态学、EMT标志物、迁移和侵袭等变化。采用酶联免疫吸附法检测肿瘤细胞中tgf - β蛋白水平，并利用特异性抑制剂SB431542探讨tgf - β信号通路在电离辐射对EMT影响中的作用。结果：总剂量为2 Gy的γ射线照射后，癌细胞呈现间充质表型，与假照射组相比，上皮标记物表达减少，间充质标记物表达增加，迁移侵袭能力增强，tgf - β蛋白水平增强。此外，IR在A549中诱导的EMT相关事件可以通过抑制tgf - β信号传导而逆转。结论：这些结果表明，tgf - β介导的EMT在ir诱导的癌细胞迁移和侵袭能力增强中起着关键作用。(C) 2011爱思唯尔公司
Purpose: To examine whether ionizing radiation enhances the migratory and invasive abilities of cancer cells through transforming growth factor (TGF-beta)-mediated epithelial-mesenchymal transition (EMT).Methods and Materials: Six cancer cell lines originating from different human organs were irradiated by Co-60 gamma-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-beta in these cancer cells were detected by enzymelinked immunosorbent assay, and the role of TGF-beta signaling pathway in the effect of ionizing radiation on EMT was investigate by using the specific inhibitor SB431542.Results: After irradiation with gamma-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-beta were enhanced. Furthermore, events associated with EMT induced by IR in A549 could be reversed through inhibition of TGF-beta signaling.Conclusions: These results suggest that EMT mediated by TGF-beta plays a critical role in IR-induced enhancing of migratory and invasive capabilities in cancer cells. (C) 2011 Elsevier Inc.