结肠癌发病率死亡率近年在中国急剧增加。化疗耐药是结肠癌预后不佳的主要原因之一。因此，寻找抗耐药的策略是结肠癌治疗的重点。本课题组前期研究中证实中药单体姜黄素诱导去甲基化酶TET1表达，抑制EMT标记物细胞内水平，抑制耐药性结肠癌细胞生长。由此，我们推测姜黄素通过TET1上调NKD2而抑制Wnt信号通路，从而抑制上皮间质转化（EMT）介导的肿瘤细胞耐药性。为验证该假说，本项目将通过肠癌细胞、肿瘤动物模型等实验来：1) 明确5-FU耐药细胞中，姜黄素能够抑制EMT介导的5-FU耐药；2)证实TET1-NKD2-Wnt信号通路抑制EMT介导的结肠癌细胞5-FU耐药；3)阐明姜黄素通过TET1调控NKD2来抑制Wnt活性，从而抑制EMT介导的5-FU化疗耐药。本项目将有助于阐明结肠癌5-FU耐药的分子机制，为姜黄素的临床运用提供坚实的理论及实验基础。

Epithelial－mesenchymal transition (EMT) plays important roles in the chemotherapy resistance in colorectal cancer. Interventions targeting EMT has been proposed as efficient approaches for the prevention and treatment of chemotherapy resistance. Our preliminary results found that curcumin could efficiently inhibit tumor cell growth both in vitro and in vivo. In addition, curcumin inhibits EMT and the activity of Wnt signaling via upregulating the expression of NKD2, an antagonist of Wnt signaling. Therefore, we proposed that curcumin promotes NKD2 expression to suppress carcinogenesis via inhibiting EMT and Wnt signaling. We would prove this hypothesis in this study by exploring the effect of curcumin on the regulation and function of NKD2 as well as other genes related with EMT and carcinogenesis and inhibits the resistance of 5-FU. By doing so, our study would provide insights to understand the mechanism of human carcinogenesis and develop more efficient anti-cancer drugs from traditional Chinese drugs.