Background: Many studies have reported that the inflammatory immune response related to TLR9  signaling activation participates in tumor development and affects the treatment outcome. RUNX3  functions as a tumor suppressor by regulating DNA methylation. RUNX3  protein plays an important role in TGF-β signaling pathway that is involved in tumor growth inhibition and apoptosis. At present, radiotherapy is still an important treatment in lung cancer, which induces immune response and affects the therapeutic outcome. The role of TLR9  signaling activation and RUNX3  in this process is not clear.
Methods: In this study, we investigated the expression of TLR9  in tumor and RUNX3  in surrounding tissues by immunohistochemical methods and analyzed the relationship on postoperative survival in lung cancer.
Results: We found that the high expression of TLR9  was the risk factor in postoperative survival of lung cancer with no difference in lifetime. The high expression of RUNX3  in lung cancer with TLR9  signaling activation was in favor of progression-free survival and overall survival in postoperative radiotherapy. It suggested that RUNX3  played an important role in lung cancer radiotherapy. In order to determine the effect of RUNX3  in lung cancer radiation with TLR9  signaling activation, we introduced 5-Aza-2ʹ-deoxycytidine (5-Aza-CdR) and exposed lung cancer A459 cells repeatedly. The high expression of RUNX3  especially RUNX3 -B in cells treated with 5-Aza-CdR was observed. We examined that 5-Aza-CdR induced more cell blocking in G2/M phase in combining irradiation.
Conclusion: The result implied that it was feasible to improve radiosensitivity of lung cancer with TLR9  signaling activation by increasing RUNX3  expression, and 5-Aza-CdR was an option in this process.
Keywords: TLR9  signaling activation, RUNX3  expression, 5-Aza-CdR, radiotherapy, lung cancer