食管癌是临床常见的恶性肿瘤，放射性125I粒子内照射支架是治疗食管癌的一种有效、微创的治疗方式。肿瘤的放射抵抗一定程度上限制了125I粒子的疗效，而肿瘤微环境与放射抵抗密切相关。TGF-β在肿瘤微环境中起中心调控作用，TGF-β/Smads信号通路是TGF-β发挥生物功能的主要通路，与上皮间质转化（EMT）、DNA损伤应答(DDR)和免疫调节有关，但在粒子治疗中的作用及机制不明。我们前期的实验发现，125I粒子可以影响食管癌组织内TGF-β表达，并诱导EMT； 125I粒子联合TGF-β受体抑制剂可提高食管癌细胞凋亡率。本研究拟进一步明确TGF-β/Smads信号通路在125I粒子治疗中对食管癌细胞EMT和DDR的影响及机制，动物水平评估干预该通路用于提高125I粒子治疗食管癌疗效的可能性，临床水平探讨TGF-β与淋巴细胞亚群变化和患者预后的关系，以寻找新的疗效预测指标和联合治疗靶点。

Esophageal cancer is a common cancer in clinic, and placement of an irradiation stent loaded with 125I seeds is an effective and minimally invasive treatment for esophageal cancer. However, the efficacy of 125I seeds can be restricted by radioresistance, which is closely related to the tumor microenvironment (TME). Transforming growth factor-β (TGF-β) acts as a central regulator of TME, and TGF-β/Smads signaling pathway is the main pathway of TGF-β. TGF-β/Smads signaling pathway was reported to be related with epithelial-mesenchymal transition (EMT)、DNA damage response (DDR), and immune regulation, while it’s roles and mechanisms in 125I seeds brachytherapy have not been thoroughly investigated. In our previous study, it was found that 125I seeds could influence the level of TGF-β in esophageal carcinoma, and induce EMT. Moreover, compared with 125I seeds brachytherapy, the combined treatment of 125I seeds brachytherapy and TGF-β receptor inhibitor could provide a higher apoptosis rate. The purposes of this study are to further demonstrate the roles of TGF-β/Smads signaling pathway in the EMT and DDR of esophageal cancer cells under 125I seeds continuous low-dose rate radiation, to evaluate the possibility of TGF-β/Smads signaling pathway intervention for efficacy improvement through animal study, and to investigate the relationship among TGF-β, lymphocyte subsets percentages, and prognosis of patients through clinical trial. It is believed that this study will provide sufficient evidences of new efficacy predict factors and therapeutic targets in the 125I seeds brachytherapy on esophageal cancer.