健脾益气、消癥散结法调控miR-155介导的肿瘤相关巨噬细胞极化抑制胃癌上皮间质转化的机制研究

项目名称： 健脾益气、消癥散结法调控miR-155介导的肿瘤相关巨噬细胞极化抑制胃癌上皮间质转化的机制研究

项目编号： No.81473605

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 刘沈林

作者单位： 南京中医药大学

项目金额： 74万元

中文摘要： 肿瘤相关巨噬细胞（TAM）类M2极化表型促进胃癌细胞上皮间质转化（EMT）是胃癌转移重要机制；通过miR-155调控TAM向M1极化，减少胃癌EMT，抑制胃癌转移是肿瘤免疫学研究热点。前期研究表明以健脾益气、消癥散结为治法的中药组方能有效抑制胃癌患者的复发转移；在移植瘤动物模型中通过提高巨噬细胞在内的免疫系统活性而抑制炎性通路，减少胃癌EMT。我们基于前期工作基础提出假说：以健脾益气、消癥散结为指导的中药组方通过调控miR-155及其靶基因促进TAM的M1型极化，抑制胃癌细胞EMT从而抗胃癌转移。本课题拟采用胃癌皮下移植瘤动物及共培养细胞模型，研究该治法下的中药组方引起的miR-155调控TAM极化的干预环节；进一步研究TAM极化改变对胃癌EMT的影响及关键分子的变化。该研究有利于明确健脾益气、消癥散结法抑制胃癌复发转移机制，诠释中医理论指导下治疗胃癌复发转移干预策略的科学性。

中文关键词： 健脾益气；消癥散结法；miR-155；胃癌转移；肿瘤相关巨噬细胞；上皮间质转化

英文摘要： One of the key mechanisms involved in gastric cancer metastasis is that tumor-associated macrophages (TAMs) with M2 polarization phenotype could promote epithelial mesenchymal transition (EMT) in gastric cancer cells. M1 polarization of TAMs induced by miR-155 can reduce EMT in gastric cancer and finally inhibit the metastasis, which now is a research focus in cancer immunology. Our previous study revealed that traditional Chinese medicines formula with effects of spleen-strengthening, Qi-invigorating and mass-eliminating could effectively reduce the recurrence of gastric cancer in patients. In the animal models with tumor xenografts, we reported that the EMT in gastric cancer decreased after the inhibition of inflammatory pathways by improving the activity of immune system which has the macrophages. Therefore, we suppose the formula could inhibit gastric cancer EMT and metastasis by promoting TAM M1 polarization through miR-155. This proposal will discover the intervention of this formula in mediating TAM polarization by regulating miR-155. Further,how TAM polarization influences gastric cancer EMT and its key factors involved in this process in animal models with gastric cancer orthotopic transplanted and co-cultured cell models will also be investigated. This study will help to specify some mechanisms in the gastric cancer metastasis inhibited by the formula, and reveal the significance of traditional Chinese medicine theory in gastric cancer relapse and metastasis. This study will help to specify some mechanisms in the gastric cancer metastasis inhibited by the formula, and reveal the significance of traditional Chinese medicine theory in gastric cancer relapse and metastasis.

英文关键词： spleen-strengthening; Qi-invigorating and mass-eliminatingprinciple;miR-155;Gastric cancer metastasis;Tumor-associated macrophages;Epithelial-mesenchymal transition