三七皂苷调控miR-18a介导的TGF-β/smads信号通路抑制肺癌转移的效应机制研究

项目名称： 三七皂苷调控miR-18a介导的TGF-β/smads信号通路抑制肺癌转移的效应机制研究

项目编号： No.81503309

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 王培伟

作者单位： 上海中医药大学

项目金额： 18万元

中文摘要： 肺癌是我国常见的恶性肿瘤之一，其发病率和死亡率均高居所有恶性肿瘤首位，转移扩散是其预后差的首要原因。miRNA的发现为肺癌发病机制的研究提供了新的思路，为肺癌诊断和治疗提供了新的策略，其网络调控在诠释肺癌转移机制的突出作用引起领域内高度关注。三七是当前研究广泛而深入的中草药，其有效抗肿瘤作用得到广泛注目，然而，其复杂的机制研究仍有待深入。我们前期研究显示三七皂苷具有显著抑制肺癌转移效果，同时miRNA表达谱芯片结果提示它能够显著调控miR-18a在肿瘤组织的表达。本项目在前期实验数据提示和引导下，拟从miRNA表达谱芯片筛选出的miR-18a入手，以实验性肺癌转移小鼠模型及肺癌细胞为对象，通过体内外研究，以对 miR-18a介导的TGF-β/smads信号通路调控为核心，进一步深入探索三七皂苷干预肺癌转移可能的分子机制，为以三七为原料抗肿瘤新药的开发和再开发提供更充实的实验依据和理论支撑。

中文关键词： 三七皂苷；肿瘤转移；肺癌；微小RNA-18a；TGF-β/smads

英文摘要： Lung cancer is one of the common malignant tumors in China, both incidence and mortality rates are the highest in all cancers, and metastasis is the primary cause of its poor prognosis. The discovery of microRNA provides new strategies and new ideas for the pathogenes, diagnosis and treatment of lung cancer, and its prominent roles in network regulation cause great concern in the field. Panax notoginseng is one of the well-studied medicinal herbs, and its effective anti-tumor effects have been attracted widely attention. However, the mechanisms underlining the effects of Panax notoginseng are very complex and require further exploration. Our preliminary studies showed that Panax notoginseng saponins presented significant effects on inhibiting lung cancer metastasis, meanwhile, miRNA microarray results suggested that it significantly down-regulated the expression of miR-18a in tumor tissue. To further explore the mechanisms underlining the action of Panax notoginseng saponins on lung cancer metastasis, we propose to investigate its effects and mechanisms via miR-18a-mediated TGF-β/smads pathway. We aim to delineate the possible molecular mechanisms of Panax notoginseng saponins in inhibiting lung cancer metastasis. We hope that our study will provide solid scientific and experimental evidence and shed novel insights into the therapeutic and preventional strategy targeting lung cancer metastasis.

英文关键词： Panax Notoginseng Saponins;Metastasis;Lung Cancer;miR-18a;TGF-β/smads