SHIP2靶向调控AKT对喉鳞癌放射敏感性的影响及机制研究

喉癌是对放射线不敏感的恶性肿瘤之一，其中放射抗拒是导致其局部复发或放疗失败的重要原因,寻求放射敏感性的可行预测指标，是增加喉癌细胞特别是辐射耐受细胞放射敏感性的关键。前期我们通过建立喉鳞癌放射抗拒株模型，通过蛋白组学技术筛选并首次发现SHIP2在喉鳞癌放射抗拒株中高表达。据此我们推测SHIP2和喉癌放疗抵抗相关。本课题拟构建SHIP2的高表达及ShRNA的慢病毒表达载体，分别转染不同放射敏感性的喉鳞癌细胞株，采用体内外试验检测其放射敏感性及生物学行为改变，分析SHIP2表达对喉癌细胞Akt磷酸化水平及下游靶基因的影响，进一步了解喉癌对放疗抵抗的内在分子机制,为放射治疗提供新的分子标记和治疗靶点。

Laryngeal cancer is one of the malignant tumor which is not sensitive to radiation, radiation resistance is the important cause of the failure of tumor local recurrence or radiation therapy, the key to increase the radiosensitivity of laryngeal cancer cells, especially the radioresistant ones is to seek feasible predictor. Previous we screening and first known SHIP2 high expression in laryngeal squamous radiation resist plant through the establishment of laryngeal cancer radiation resistance strain model by proteomic analysis. We hypothesized that SHIP2 associated with radioresistant of laryngeal cancer. This topic plans to build the high expression of SHIP2 and ShRNA slow virus expression vector transfected different radiosensitivity of laryngeal squamous cell lines, using in vivo and in vitro experiment to test its radiation sensitivity and cell biology behavior change, and further detect modification of expression of SHIP2 on Akt phosphorylation level and downstream target genes in laryngeal cancer cells. To learn more about laryngeal cancer molecular mechanism of radiation resistance, offers a new molecular markers and therapeutic targets for radiotherapy.