中国食管癌死亡率居全世界首位，探索食管癌有效疗法迫在眉睫。死亡受体配体 (TRAIL)可诱导肿瘤细胞凋亡而对正常细胞没有明显毒性而受到广泛关注。但是，部分食管癌细胞由于死亡受体DR5或DR4表达缺失等因素对TRAIL作用不敏感，限制了其临床应用。本课题组前期研究发现香加皮杠柳苷 (Periplocin) 可部分通过抑制Wnt/β-catenin信号通路活性抑制多种肿瘤细胞增殖，且可增加食管癌细胞DR4和DR5的表达，具有成为TRAIL增敏剂的潜能。本项目拟应用原子力显微镜、荧光素酶报告基因、电泳迁移率实验 和免疫荧光等多种分子和细胞生物学技术探讨Periplocin对食管癌细胞TRAIL耐药的逆转作用，阐明Wnt/β-catenin信号通路在此过程中的作用及机制，并观察Periplocin与TRAIL联合应用对食管癌裸鼠移植瘤的抑制作用，为Periplocin和TRAIL联合应用奠定基础。

The mortality rate of esophageal cancer in China is the first place in the world and the urgent aim is to explore the effective therapy for esophageal cancer. The death receptor ligand (TRAIL) has attracted extensive attention because it can induce apoptosis of tumor cells while has no apparent toxicity to normal cells. However, a few esophageal cancer cell lines are not sensitive to TRAIL due to loss of death receptor 5 or 4 and some other factors, leading to the limitation of the clinical application. The previous studies in our research team found that periplocin can inhibit the proliferation, induce apoptosis of a variety of tumors and increase the expression of DR4 and DR5 of esophageal carcinoma cells partly through repressing the activity of the Wnt /β-catenin signaling pathway, and it maybe a potential sensitizer of TRAIL. A variety of molecular and cell biology technology, for example, atomic force microscopy (AFM), luciferase reporter gene, electrophoresis mobility shift assay (EMSA), immunofluorescence and so on will be applied to our study to explore the reversal effect of periplocin on esophageal cancer cell resisted to trail, clarify the effect and activity of Wnt /β-catenin signaling pathway in this process, observe the inhibitory effect of periplocin combined with TRAIL on esophageal cancer in nude mice, and finally build the foundation for clinical application for combination of perilocin and TRAIL.