Next Generation Sequencing of H292 cell line cultured with CAFs CM or SL-CAFs CM

Cancer cell radioresistance is the primary cause of the decreased curability of non-small cell lung cancer (NSCLC) observed in patients receiving definitive radiotherapy (RT). Following RT, a set of microenvironmental stress responses is triggered, including cell senescence. However, cell senescence is often ignored in designing effective strategies to resolve cancer cell radioresistance. Herein, we identified the senescence-like characteristics of cancer-associated fibroblasts (CAFs) post RT and clarified the formidable ability of senescence-like CAFs in promoting NSCLC cells proliferation and radioresistance through the JAK/STAT pathway. Specific induction of senescence-like CAFs apoptosis using FOXO4-DRI, a FOXO4-p53 interfering peptide, resulted in remarkable effects on radiosensitizing NSCLC cells in vitro and in vivo. In addition, our study also discovered the obvious therapeutic effect of FOXO4-DRI on alleviating radiation-induced pulmonary fibrosis (RIPF) by targeting senescence-like fibroblasts in vivo. In conclusion, by targeting senescence, we offer a new strategy which simultaneously decreases radioresistance of NSCLC and the incidence of RIPF. mRNA profiles of 6 samples (H292 cell line, CAFs CM group and SL-CAFs CM group, 3 replicates per group).