Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, Yuseong, Daejeon 305-600, Korea.
Int J Mol Med. 2010 Apr;25(4):517-23. doi: 10.3892/ijmm_00000372.
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 G(2)/M arrest after 12 h of irradiation (5 Gy), reaching 60% of G(2)/M phase arrest. A549 cells also showed a significant G(2)/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 approximately 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.
癌细胞和正常组织对电离辐射的敏感性或抗性在肺癌治疗的临床环境中起着重要作用。然而，迄今为止，内在放射敏感性的确切分子机制尚未得到很好的解释。在这项研究中，我们比较了两种非小细胞肺癌（NSCLC）H460 和 A549 的放射敏感性或放射抗性，并研究了赋予放射抗性的信号通路。H460 细胞在照射（5 Gy）12 小时后显示出明显的 G2/M 期阻滞，达到 60%的 G2/M 期阻滞。A549 细胞在暴露 12 小时后也显示出明显的 G2/M 期阻滞；然而，这种阻滞在暴露 24 小时后完全消失。A549 细胞中 PTEN 的甲基化 CpG 位点比 H460 细胞高，这与某些癌细胞的肿瘤放射抗性有关，A549 细胞中的平均甲基化程度比 H460 细胞高约 4.3 倍。结果，A549 中的 PTEN 表达低于 H460。进行 Western blot 分析，我们发现 PTEN 作为 pAkt 的负调节剂起作用，pAkt 作为 p53 表达的负调节剂起作用。根据上述结果，我们得出结论，H460 细胞中显示的放射敏感性可能是由于通过 p53 信号通路表达更高的 PTEN。
