Mechanism of action of a Traditional Chinese Medicine Compound

来源 :22nd Asia Pacific Cancer Conference(第22届亚太抗癌大会) | 被引量 : 0次 | 上传用户:zhangersong
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Objective: To combine genomics, systems biology, and network pharmacology methods to explore the inhibitory effect of JinLong Capsules on glioblastoma, and determine the mechanisms,and to offer a reference for other studies on Traditional Chinese Medicine compounds.Methods: The glioblastoma in situ nude mice models with red fluorescent protein were established.The models were administered with vehicle, Jin-Long Capsules (0.75 and1.5 g·kg 1), and temozolomide capsules (0.096 g.kg-1),respectively, for 28 d.The tumor size and weight were monitored by Fluor Vivo imaging technology in real time.After 28 d, mice of the four groups were killed, and the intracranial tumors were obtained and weighed.For the mice administered with vehicle and 0.75 g.kg-1 Jin-Long Capsules, Affymetrix Human Genome U133 Plus 2.0 gene chip was used for gene screening of the brain tumor tissues in nude mice.The genome results were analyzed by systems biology and network pharmacology methods.First,differentially expressed genes were identified based on fold change between the two groups.Then, to identify upstreamregulators of the response signatures, the differentially expressed genes were subjected to interactome analysis by one-step over connectivity test and multi-step hidden nodes algorithm.A set of genes preferentially connected to differentially expressed genes was generated via direct interactions and pathways (i.e.,topologically significant genes).Concurrent pathway enrichment analysis on key pathways, processes, and functional units of both differentially expressed genes and topologically significant genes was then performed to identify the most likely signaling pathways connecting regulators and effect or genes.Finally,condition-specific networks (called causal networks) were constructed to model molecular events, using a set of manually annotated protein interactions, pathways, and proteins and a toolkit of algorithms and filters.
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