金龙胶囊抗脑肿瘤的系统生物学研究

Study of anti-cancer traditional Chinese medicine using systems biology technology

  • 摘要:
      目的  利用系统生物学技术分析中药复方金龙胶囊抗脑肿瘤的分子机制。
      方法  取金龙胶囊组及空白对照组小鼠的原位脑肿瘤组织样本进行基因芯片检测,通过比对获取差异基因;使用一步过连通测算和多步骤隐藏节点测算获得拓扑基因;采用富集分析法分析其生物功能;借助MetaCore平台构建分子机制网络图。
      结果  与对照组相比,金龙胶囊组共有37个差异基因(倍数>2),106个拓扑基因。金龙胶囊的靶点主要集中在细胞粘附和凋亡、免疫应答、神经组织发育等。
      结论  金龙胶囊通过诱导神经细胞特有基因表达和抑制干扰素信号转导发挥抗脑肿瘤作用。

     

    Abstract:
      Objective  This article focuses on the research of molecular mechanism of brain tumor treatment using the Jinlong capsule via system biology technology.
      Methods  Human Genome U133 Plus 2.0 gene chip was used to detect the genes of samples, including the brain tumor tissues of nude mice after Jinlong capsule intervention and those of blank control group mice. Differentially expressed genes were identified based on fold change between the two groups. To identify the upstream regulators of the response signatures, the differentially expressed genes were subjected to interactome analysis by one-step overconnectivity test and multi-step hidden node algorithm. A set of genes preferentially connected to differentially expressed genes via direct interactions and pathways (called topologically significant genes) was generated. Concurrent pathway enrichment analysis on key pathways, processes, and functional units of both differentially expressed genes and topologically significant genes was performed to identify the most likely signaling pathways connecting regulators and effector genes. Finally, condition-specific networks (called causal network) were built to model molecular events by using a set of manually annotated protein interactions, pathways, and proteins and a toolkit of algorithms and filters on MetaCore platform.
      Results  A total of 37 differentially expressed genes have been identified between Jinlong capsule-treated sample and vehicle sample with fold change of 2. Connection analysis identified 106 topologically significant genes. The main feature of the causal network is stimulation of neural cell specific genes that regulate normal cell physiology, particularly developmental processes and apoptosis. Another important effect of the Jinlong capsule is its inhibition of the gene markers of interferon response, suggesting signaling inhibition, followed by de-activation of immune response.
      Conclusion  Jinlong capsule exerts an anti-neoplastic effect by inducing stimulation of neural cell and by inhibiting interferon signal transduction.

     

/

返回文章
返回