Huang H.,Beijing Vital Medicine Research and Development Center |
Huang H.,Beijing Jiansheng Pharmaceutical Co. |
Qu Y.,Beijing Vital Medicine Research and Development Center |
Qu Y.,Beijing Jiansheng Pharmaceutical Co. |
And 8 more authors.
Chinese Journal of Clinical Oncology | Year: 2014
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 Meta-Core 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.