基于UCA1/miR-1信号轴调节食管癌细胞与CAFs能量交互研究健脾和胃法治疗食管癌的分子机制

食管癌发病率高、预后差，癌相关成纤维细胞（CAFs）与肿瘤细胞间能量交互参与肿瘤发展进程，UCA1/miR-1信号轴调控两者的能量代谢。健脾和胃法及其代表方六君子汤是食管癌常用治法和方药，能影响食管癌细胞能量代谢，干预UCA1、miR-1及其上下游分子表达和其他多个影响食管癌进程的信号通路。基于此，本课题主要围绕“健脾和胃法及方药可通过干预UCA1/miR-1信号轴调控食管癌细胞与CAFs能量交互起到治疗食管癌作用”这一假说开展研究。应用4NQO诱导的食管癌动物验证健脾和胃法代表方六君子汤可影响食管癌组织能量代谢和UCA1/miR-1信号轴，在体外应用细胞共培养、细胞转染、能量代谢分析等技术确认该方可通过UCA1/miR-1信号轴干预CAFs与食管癌细胞之间能量交互，最后应用移植瘤动物进一步确证。由此探索健脾和胃法治疗食管癌机制，为临床应用提供依据，为研究中医治疗食管癌作用机制展开新视觉。

Esophageal cancer has high incidence rate and poor prognosis. The energy interaction between cancer-associated fibroblasts (CAFs) and tumor cells is involved in the development of tumors, and the UCA1/miR-1 signal axis regulates the energy metabolism between the two. Invigorating spleen for harmonizing stomach treatment is a common treatment and prescription for esophageal cancer, which can affect the energy metabolism of esophageal cancer cells, interfere with the expression of UCA1, miR-1 and its upstream and downstream molecules and other signal pathways that affect the progression of esophageal cancer. Based on this, this research will mainly focus on the scientific hypothesis that ‘UCA1/miR-1 signal axis is an important way to regulate the energy interaction between esophageal cancer cells and CAFs, and invigorating spleen for harmonizing stomach treatment and prescriptions may play a role in treating esophageal cancer by interfering with the UCA1/miR-1 signal axis to regulate the energy interaction between esophageal cancer cells and CAFs’. Firstly, 4NQO induced esophageal cancer animal model will be used to observe the effect of Liujunzi Decoction which is invigorating spleen for harmonizing stomach treatment representative prescription on energy metabolism and UCA1 / miR-1 signal axis of esophageal cancer tissue. In vitro,cell co-culture, energy metabolism analysis, cell transfection and other technologies will be applied to confirm that the formula can intervene the energy interaction between CAFs and esophageal cancer cells through UCA1 / miR-1 signal axis. Finally, Xenograft model will be used to confirm it.In order to explore the mechanism of invigorating spleen for harmonizing stomach treatment for esophageal cancer, and provide evidence for its clinical application. It opens a new perspective for studying the mechanism of traditional Chinese medicine in treating esophageal cancer