放射性碘抵抗是分化型甲状腺癌（DTC）131I治疗领域亟需解决的主要难题。研究发现，MAPK、PI3K-AKT-mTOR等信号通路的激活、表观遗传学改变均与DTC的发生、碘代谢相关基因沉默、恶性临床病理特征密切相关。受国家自然科学基金（编号：30700187和81271609）连续资助，我研究小组陆续证实了钠/碘转运体在介导肿瘤细胞摄碘中的关键作用及激酶抑制剂对DTC碘和葡萄糖代谢的有效调控。在此基础上，本研究拟选取多种已知突变DTC细胞系，通过RT-PCR、Western blot、免疫荧光、放射性核素摄取/流出、克隆形成等体外实验和小动物SPECT、小动物PET、核素治疗等体内实验，在基因、蛋白和功能水平上全面评价激酶抑制剂和表观遗传学药物是否存在协同再分化作用并揭示其潜在机制，分析其效能与DTC分子分型之间是否存在相关性，为分子影像和基因检测指导DTC的精准再分化治疗奠定基础。

Radioiodine-refractoriness represents a currently major challenge in the 131I therapy of differentiated thyroid carcinoma (DTC). The constitutive activation of signaling pathways, including MAPK, PI3K-AKT-mTOR, etc, plays a vital role in tumorigenesis, silencing of various thyroid iodide-metabolizing genes and the presence of malignant clinicopathologic features, which have also been demonstrated to be associated with epigenetic changes. Continuously sponsored by the National Natural Science Foundation of China (No.30700187 and 81271609), our group has successively achieved promising findings in many basic and clinical researches. Given the encouraging data of our preliminary study recently, which initially showed increased radioiodine uptake induced by sodium/iodide symporter gene transfer and successful modulation of iodide- and glucose-handling gene expression regulated by kinase inhibitors, the present study is designed to investigate the synergistic redifferentiation effect of kinase inhibitor and epigenetic drug in a variety of authenticated thyroid carcinoma cell lines harboring known gene alterations in vitro and in vivo. The effect of such novel redifferentiation strategy as well as the association between the effect and molecular genotype will be evaluated on gene, protein and functional levels using RT-PCR, Western blot, immunofluorescence, radioisotope uptake/efflux, clonogenic assay, micro-SPECT, micro-PET, and radionuclide therapy. Our project also aims at revealing the underlying mechanism and laying a foundation for molecular imaging and gene analysis in the precise redifferentiation treatment of DTC.