| 引用本文:魏华民1，俞静1，郭秋均2，刘瑞2，花宝金2.肺转移前微环境体外模型的建立与双参颗粒干预机制[J].世界中医药,2021,(06):. |
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| 肺转移前微环境体外模型的建立与双参颗粒干预机制 |
| Establishment of an in Vitro Model of Microenvironment before Lung Metastasis and the Intervention Mechanism of Shuangshen Granule |
| 投稿时间：2020-11-25 |
| DOI：10.3969/j.issn.1673-7202.2021.06.009 |
| 中文关键词: 肺转移前微环境 双参颗粒 体外模型 小鼠 S1pr1-stat3信号通路 |
| English Keywords:Pre-lung metastasis microenvironment Shuangshen Guanule In vitro model Mouse S1pr1-stat3 signaling pathways |
| 基金项目:国家自然科学基金项目(81904102,81603601);北京市自然科学基金项目(7184203);中国中医科学院优秀青年科技人才(创新类)培养专项(ZZ13-YQ-023) |
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| 中文摘要: |
| 目的:构建肺转移前微环境体外模型,观察S1pr1-stat3信号通路在模型成熟过程中的作用,同时验证双参颗粒对该模型的干预作用,探讨其可能的机制。方法:体外构建小鼠Lewis肺癌细胞和原代骨髓细胞共培养模型,并用S1pr1激活剂SEW2871干预髓系细胞分化的过程,观察相关蛋白MMP9、Lox、Version及Fibronectin的表达情况,并检测模型中骨髓来源的抑制性细胞(MDSCs)细胞的分化情况及双参颗粒对模型的干预效果。结果:S1pr1可以明显促进肺转移前微环境体外模型的成熟构建,S1pr1-stat3是该模型成熟的关键信号通路,双参颗粒不仅显著降低模型中该信号通路相关蛋白的表达,同时对微环境成熟的关键蛋白的表达也具有抑制作用,还可显著降低该信号通路相关的骨髓细胞向MDSCs细胞的分化(P<0.05),同时对转移前微环境中部分肿瘤源性细胞因子如粒细胞-巨噬细胞集落刺激因子（GM-CSF)及转化生长因子（TGF-β)有显著抑制作用(P<0.05)。结论:双参颗粒通过抑制S1pr1-stat3信号通路及部分肿瘤源性细胞因子的表达,抑制肺转移前微环境模型的成熟。 |
| English Summary: |
| To establish an in vitro model of microenvironment before lung metastasis，and explore the efficacy of S1pr1-stat3 signaling pathway in the mature process and at the same time to verify the intervention effect of Shuangshen Granule (SSG) on the model，and explore its potential mechanism.Methods:Mouse Lewis lung cancer cells and primary bone marrow cells were co cultured in vitro and the differentiation of bone marrow cells were intervened by s1pr1 activator Sew2871.The expression of MMP9，LOX，Version and Fibronectin，and the differentiation of MDSCs cells of the model were observed and the intervention effect of SSG on the model were detected.Results:S1pr1 could significantly promote the construction of the in vitro model of microenvironment before lung metastasis，and S1pr1-stat3 was the key signal pathway for the maturation of the model.SSG not only significantly reduced the expression of the signal pathway related proteins in the model，but also inhibited the expression of key proteins in microenvironment maturation，and significantly reduced the differentiation of bone marrow cells to MDSCs under the effect of signal pathway (P<0.05).Meanwhile，it also significantly inhibited some tumor-derived cytokines such as GM-CSF and TGF-β in the pre metastasis model (P<0.05).Conclusion:Shuangshen Granule can inhibit the maturation of the pre-lung metastasis microenvironment model before lung metastasis by inhibiting the expression of s1pr1-stat3 signal pathway and some tumor-derived cytokines. |
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