IONIZING RADIATION PROMOTES MIGRATION AND INVASION OF CANCER CELLS THROUGH TRANSFORMING GROWTH FACTOR-BETA-MEDIATED EPITHELIAL MESENCHYMAL TRANSITION

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.