NF2作为调节肺癌放疗疗效新靶向基因的研究

Radiotherapy is one of important stragyies of lung cancer, a frequent occurrence of radioresistance in patiets treated with radiotherapy limits its application and results in treatment failure. In the preliminary studies, we identified a novel protein, NF2/Merlin, related to radiotherapy of lung cancer by techinques of clinical proteomics. Further studies suggested a positive relationship bwteen radiosenstivity and expression level of a tumor suppressor gene NF2 in lung cancer cell lines texted, increased or decreased expression NF2 expression caused a significant alteraions of lung cancer radiosensitivity, these findings indicate that NF2 is possibly a novel target gene involving in regulation of radiosenstivity and radiotherapy effecincy in lung cancer. Therefore, this project will deeply study, based on a large numbers of preliminary results, thr role of NF2 and the underlying mechanism(s) in mediating radiotherapy of lung cancer by in vitro cell line models and in vivo animal models. It is expected that these studies will provide evidence and fundation for further exploration of potential application of NF2 as a novel target gene in radiotherapy of lung cancer and are of value and sinificance either in basic research and clinical application in future in lung cancer radiotherapy.

放射治疗为肺癌的重要治疗手段之一，然而治疗中肺癌病人常常产生辐射耐受性而限制了肺癌放射治疗广泛应用或者导致治疗失败。在采用蛋白组学筛选肺癌辐射治疗相关蛋白研究中研究首次发现一个新的肺癌辐射敏感性相关蛋白NF2，进一步研究发现肺癌细胞中NF2的表达水平与其放射敏感性显现正相关，人为提高或降低NF2表达水平可以明显地改变肺癌细胞的放射敏感性，提示NF2可能是重要的调节肺癌放射治疗敏感性和治疗疗效的新基因。为此，本项目将在大量预实验研究的基础上，采用肺癌体外细胞模型及体内动物模型深入研究NF2在肺癌放射治疗的作用和机制。期望通过一系列临床前研究，为NF2作为肺癌放射治疗新的靶向基因在临床肺癌放射治疗中的应用提供必要的研究依据和实验基础。因此，这项研究无论在肺癌放射治疗的基础研究还是在将来临床研究上的应用都具有重要的临床意义和研究价值。

首次发现了NF2作为辐射应答基因，其表达产物Merlin蛋白在辐射暴露后上调，并且NF2/Merlin含量的多少与辐射敏感性正相关。.在肺癌细胞系和肺癌裸鼠移植瘤模型体内，首次证明了Merlin蛋白在电离辐射后除胞内磷酸化介导凋亡外，还有一部分释放到细胞外，并发挥活性。.胞外释放的Merlin蛋白起着怎样的作用有待进一步的研究。.本项目成功验证了NF2可以作为新的放射治疗调节靶向基因，为其在临床肺癌放射治疗中的应用提供理论依据。