[en] The sensitivity or resistance of cancer cells and normal tissues to ionizing radiation plays an important role in the clinical setting of lung cancer treatment. However, to date the exact molecular mechanisms of intrinsic radiosensitivity have not been well explained. In this study, we compared the radiosensitivity or radioresistance in two non-small cell lung cancers (NSCLCs), H460 and A549, and investigated the signaling pathways that confer radioresistance. H460 cells showed a significant G2/M arrest after 12 h of irradiation (5 Gy), reaching 60% of G2/M phase arrest. A549 cells also showed a significant G2/M arrest after 12 h of exposure; however, this arrest completely disappeared after 24 h of exposure. A549 has higher methylated CpG sites in PTEN, which is correlated with tumor radioresistance in some cancer cells, than H460 cells, and the average of the extent of the methylation was ∼4.3 times higher in A549 cells than in H460 cells. As a result, PTEN expression was lower in A549 than in H460. Conducting Western blot analysis, we found that PTEN acted as a negative regulator for pAkt, and the pAkt acted as a negative regulator for p53 expression. According to the above results, we concluded that the radiosensitivity shown in H460 cells may be due to the higher expression of PTEN through p53 signaling pathway. The expression of the Wnt-antagonist Dickkopf gene (DKK) is downregulated in several types of tumors as a consequence of epigenetic DNA modification; four DKK members, DKK1, DKK2, DKK3, and DKK4, have been identified. In this study, we investigated another function of DKK3 in non-small cell lung cancer H460 cells, in which DKK3 was hypermethylated (44%) but still expressed, by interfering with DKK3 expression using DKK3-silencing RNA (SiRNA). We found that knockdown of DKK3 expression by DKK3 SiRNA transfection led to the detachment of H460 cells from the bottom of the culture plate and caused apoptosis. The expression of cyclindependent kinases D1 and E were increased by DKK3 knockdown, indicating that cells with blocked DKK3 expression entered the apoptotic pathway. We also found that the intracellular level of reactive oxygen species was higher in cells with blocked DKK3 expression than in normal H460 cells, and levels of p53, p21, and Bax were also increased by the gene knockdown. These results indicate that DKK3 acts as an antiapoptotic molecule by decreasing the intracellular level of reactive oxygen species