食管腺癌作为第二大类型食管癌呈逐年增多的趋势，遗憾的是仅有30%～40%的患者可进行手术治疗，化疗是食管腺癌的重要治疗策略之一，但化疗耐药问题亟待解决。我们前期研究发现，补骨脂素干预食管腺癌耐药细胞后可在一定程度上逆转耐药，同时我们开展的补骨脂素对食管腺癌细胞 miRNA 网络调控的预实验发现补骨脂素可显著上调 miR196a 的表达水平，文献报道上调 miR196a 可下调 HOXB7 的表达，HOXB7的表达下降可抑制 HER2 信号相关通路而逆转化疗耐药。因此，我们提出假说：补骨脂素可能通过调控miR196a-HOXB7-HER2网络逆转食管腺癌顺铂的耐药。为验证此假说，拟分别构建顺铂敏感及耐药的食管腺癌细胞株和肿瘤异种移植小鼠模型，应用基因过表达与敲除、免疫荧光、核酸锁定原位杂交、qRT-PCR等技术，在细胞和动物水平上，揭示补骨脂素逆转食管腺癌顺铂耐药的分子机制。

Esophageal adenocarcinoma(EA) is the second kind of esophageal cancer and rising rapidly, unfortunately, there are only 30-40% patients good for operation. Chemotherapy plays an important role in the treatment of EA. However, the resistant to chemotherapy drug is a big problem. Our previous study found that, cisplatin will play well in EA cisplatin resistant cells after the intervention of psoralen and the expressing of miR196a increased as well, but the mechanism is unknown. Some Research shows that the target gene of miR196a is HOXB7 and HOXB7 increase the expression of HER2. Therefore, we hypothesize that: psoralen may reverse the resistant of cisplatin in the treatment of by regulation the network of miR196a-HOXB7-HER2. To confirm this hypothesis, we establish cisplatin sensitive or resistant EA cell lines and the tumor xenograft mouse models, we will reveal the mechanisms of psoralen in the effect of miR196a- HOXB7- HER2 by overexpression,knockout, immunofluorescence, locked nucleic acid in situ hybridization, qRT-PCR, Western blot technique in vitro and in vivo.The study is expected to elucidate the effects and mechanisms of psoralen, and thus to provide new ideas and theoretical basis for the treatment of EA.