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一贯煎通过LOXL2通路抑制肝癌干细胞治疗肝癌的机制研究

一贯煎通过LOXL2通路抑制肝癌干细胞治疗肝癌的机制研究
  • 导航:首页 > 科学基金
  • 批准号:81673728
  • 批准年度: 2016年
  • 学科分类:中西医结合临床基础(H2902) |
  • 项目负责人:朱英
  • 负责人职称:主任医师
  • 依托单位:大连医科大学
  • 资助金额:57万元
  • 项目类别:面上项目
  • 研究期限:2017年01月01日 至 2020年12月31日
  • 中文关键词: 一贯煎;LOXL2;肝癌;干细胞;治疗
  • 英文关键词:Yi Guan Jian;LOXL2 Pathway; Liver Cancer Stem Cells; Liver Cancer

项目摘要

中文摘要

肝癌发病率高、进展迅速,晚期肝癌以肝肾阴虚为主要中医证型,一贯煎是滋阴疏肝代表方剂。临床研究发现,一贯煎对晚期肝癌具有较好治疗作用,但详细机制尚不清楚。本课题组前期研究显示,一贯煎能够抑制肝癌干细胞增殖,并且抑制LOXL2在肝组织和血清中的表达,而LOXL2对启动肝癌侵袭和进展的肝癌干细胞具有调控作用。本课题旨在研究:①筛选肝癌干细胞,检测一贯煎通过LOXL2通路影响肝癌干细胞增殖作用;应用指纹图谱和荧光素酶报告基因系统检测一贯煎作用于LOXL2的主要活性成分。②应用肝癌干细胞建立小鼠肝癌模型,体内研究证实一贯煎通过LOXL2通路抑制肝癌作用;应用代谢组学方法,进一步分析一贯煎治疗肝癌小鼠中与LOXL2相关肿瘤微环境代谢变化及作用机制。③在上述研究基础上,应用网络药理以发现一贯煎成分在肝癌网络中与LOXL2相关的关键节点基因,阐明一贯煎活性成分通过LOXL2通路上多靶点治疗肝癌的作用机制。

英文摘要

Liver cancer has a high incidence and processes rapidly. Yin deficiency of both liver and kidney is the main Traditional Chinese Medicine syndrome type in advanced liver cancer. Yiguanjian is a representative prescription of nourishing Yin of liver. According to some clinical researches, Yiguanjian had significant effects on treating advanced liver cancer, while detailed mechanisms remain unclear. Our previous studies indicated that Yiguanjian could inhibit proliferation of liver cancer stem cells, and inhibit LOXL2 expression in both liver tissue and serum. LOXL2 is crucial in regulating liver cancer stem cells, which could promote liver cancer metastasis and progression. The study aims to: ① select liver cancer stem cells and verify Yiguanjian could affect proliferation of liver cancer stem cells through LOXL2 pathway. Use fingerprint and luciferase reported gene assay to test main active ingredients of Yiguanjian, which could exert impacts on LOXL2 pathway; ② establish the mice model of liver cancer by liver cancer stem cells and prove Yiguanjian could suppress liver cancer through LOXL2 pathway in vivo. Furthermore, use metabonomics to analyze changes of cancer microenvironment and mechanism related to LOXL2 in the treatment of Yiguanjian towards mice with liver cancer; ③ find key node genes of Yiguanjian related to LOXL2 pathway in liver cancer network through network pharmacology based on researches mentioned above. So that to illuminate the mechanism of Yiguanjian treating liver cancer with active ingredients on multiple targets via LOXL2 pathway.

评估说明

    国家自然科学基金项目“一贯煎通过LOXL2通路抑制肝癌干细胞治疗肝癌的机制研究”发布于爱科学iikx,并永久归类于相关科学基金导航中,仅供广大科研工作者查询、学习、选题参考。国科金是根据国家发展科学技术的方针、政策和规划,以及科学技术发展方向,面向全国资助基础研究和应用研究,发挥着促进我国基础研究源头创新的作用。国科金的真正价值在于它能否为科学进步和社会发展带来积极的影响。

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