Objective: Radioresistance-induced locoregional recurrence remains a major cause of low survival rates. However, the mechanism of treatment failure in these lung cancer patients has not been determined. In the current study, we tried to explore the potential molecular mechanism.
Methods: The fractionated irradiations were continued until the total concentration reached 80 Gy, and we established radioresistant subclones derived from A549 lines (designated as A549/R). The MTT assay, wound healing assay, transwell assay, and soft agar colony formation assay were employed to detect the proliferation, migration, invasion, and clonogenicity of the cells, respectively. Western blot and Fluorescence Activating Cell Sorter (FACS) indicated the expression of the markers.
Results: A549/R cells proliferated more slowly than the parental A549 cells. A significant acceleration in cell migration and invasion was revealed in A549/R cells compared with A549 cells. The expression levels of mesenchymal markers (N-cadherin, vimentin, claudin-1, and Snail) increased, while epithelial markers (E-cadherin and β-catenin) decreased in A549/R cells. Meanwhile, the expression levels of stemness markers (Oct4, Notch1, and CD133) increased in A549/R cells, and A549/R cells showed more sphere-forming activity compared with A549 cells.
Conclusion: Fractionated irradiation could promote epithelial-mesenchymal transition and enhance the migration, invasion, and stemness-like properties in A549 cells, elucidating the possible radioresistance mechanisms of the cancer cells.
Keywords: Epithelial-mesenchymal transition; fractionated irradiation; non-small cell lung cancer; radio-resistance; stemness-like properties.
© 2021 by the Association of Clinical Scientists, Inc.