TGF-β/Akt/Smad signaling regulates ionizing radiation-induced epithelial-mesenchymal transition in acquired radioresistant lung cancer cells

作者：Yongchun Zhou, Lingli Liao, Nan Su, Hua Huang, Yaoguo Yang, Yan Yang, Gengming Wang, Hongbo Xu, Hao Jiang · 发表于：Radiation Medicine and Protection · 年份：2022 · DOI：10.1016/j.radmp.2022.05.003 · 被引用次数：4 · 研究领域：Cancer Cells and Metastasis、TGF-β signaling in diseases、Cancer, Hypoxia, and Metabolism

To define the properties of lung cancer cells that resisted conventionally fractionated radiation exposure. Acquired radioresistant lung cancer cell line A549 was constructed by X-ray irradiation with a clinical conventional fraction dose of 2 Gy daily during 30 fractions. Cell morphology, molecular markers, migration capacity and invasion potential were evaluated by the microscope, Western blot, immunofluorescence, wound healing test and transwell chamber assay, respectively. Radioresistant A549 cells shifted from an epithelial to a mesenchymal morphology, termed as epithelial-mesenchymal transition (EMT), and was accompanied by decreased expressions of epithelial markers (F = 4.568, P < 0.05) and increased expression of mesenchymal markers (F = 4.270, P < 0.05), greater migratory and invasive capabilities (t = 6.386, 5.644, P < 0.05). The expression of TGF-β, and phosphorylated levels of Akt and Smad3 were also enhanced (F = 6.496, 4.685, 3.370, P < 0.05). Furthermore, the EMT phenotype induced by radiation could be reversed through inhibition of TGF-β, Akt or Smad3, indicating a functional relationship between them. EMT mediates acquired radioresistance of lung cancer cells induced by IR with clinical parameters, and the crosstalk mode of TGF-β/Akt/Smad signaling plays a critical regulatory role in this process.