Tiam1调控JNK通路对喉癌放疗敏感性的影响及机制研究

Tiam1 plays an important role in the development of malignant tumor. JNK/ATF-2 signaling pathway is closely related to the radiotherapy sensitivity. Tiam1 is an important regulation factor of JNK/ATF-2 signaling pathway. We have confirmed that Tiam1 is overexpressed in the laryngeal carcinoma, and have an effect on the prognosis of laryngeal carcinoma in our previous study. Radiotherapy, as a major treatment of laryngeal carcinoma, hence, we conduce that Tiam1 may affect the radiotherapy sensitivity of laryngeal carcinoma through JNK/ATF-2 signaling pathway. We plan to do the study both in vitro and in vivo. Firstly, we respectively upregulate or downregulate Tiam1 expression through plasmid transfection or RNA interference technique. The effect of Tiam1 expression on radiotherapy sensitivity is studied through RT-PCR, Western blot, colony forming experiment, flow cytometry and TUNEL experiment. Secondly, we downregulate JNK and ATF-2 expression through RNA interference technique, and we study whether Tiam1 can affect the radiotherapy sensitivity through JNK/ATF-2 signaling pathway. This study will first clarify the effect and mechanism of Tiam1 on radiotherapy sensitivity, and look for new theoretical basis on radiotherapy sensitivity of laryngeal carcinoma.

Tiam1在恶性肿瘤的发生发展中起重要作用。JNK/ATF-2信号通路与恶性肿瘤的放疗敏感性密切相关，而Tiam1是JNK/ATF-2信号通路的重要调节因子。我们前期研究发现：Tiam1在喉癌组织中呈高表达，其能显著影响喉癌病人的预后。而放疗是喉癌的主要治疗方法之一。因此，我们推测Tiam1可能通过调控JNK通路影响ATF-2的表达进而影响喉癌的放疗敏感性。本项目从体外及体内水平，首先通过质粒转染及RNA干扰技术分别上调及下调Tiam1的表达，运用RT-PCR、Western blot、集落形成实验、流式细胞术及TUNEL检测等技术研究Tiam1的表达对放疗敏感性的影响；继而通过RNA干扰技术分别沉默JNK及ATF-2在喉癌中的表达，研究Tiam1是否通过JNK/ATF-2通路影响放疗敏感性。本项目首次探讨Tiam1对喉癌放疗敏感性的影响及相关机制，为喉癌放疗敏感性研究奠定了新的理论基础。