Fractionated ionizing radiation facilitates interferon‐γ signaling and anticancer activity in lung adenocarcinoma cells

Abstract

AbstractFractionated ionizing radiation (FIR) is a radiotherapy regimen that is regularly performed as part of lung cancer treatment. In contrast to the growth inhibition caused by DNA damage, immunomodulation in post‐irradiated cancer cells is not well documented. Interferon (IFN)‐γ confers anticancer activity by triggering both growth inhibition and cytotoxicity. This study investigated the priming effects of FIR with immunomodulation on the anticancer IFN‐γ. Cell morphology, cell growth, and cytotoxicity were observed in FIR‐treated A549 lung adenocarcinoma. Induction of p53 and epithelial–mesenchymal transition (EMT) were monitored. Following FIR, activation of IFN‐γ signaling pathways were detected. FIR caused changes in cell morphology, inhibited cell growth, and induced cytotoxicity. While p53 was induced by FIR, no epithelial–mesenchymal transition could be found. Following IFN‐γ stimulation, FIR‐induced p53‐associated cell cytotoxicity was significantly enhanced. Additionally, FIR increased the downstream response to IFN‐γ by facilitating IFN‐γ‐induced signal transducer and activator of transcription 1 (STAT1) signaling without affecting the receptor expression. FIR‐facilitated STAT1 activation through the mechanism involving mitogen‐activated protein kinase activation and Src‐homology 2 domain‐containing tyrosine phosphatase 2 inactivation. These results demonstrate the FIR‐facilitated IFN‐γ signaling and its anticancer activity.