BACKGROUND As an effective prescription for gastric cancer (GC), Compound Kushen Injection (CKI) has been widely used even though few molecular mechanism analyses have been carried out. METHODS In this study, we identified 16 active ingredients and 60 GC target proteins. Then, we established a compound-predicted target network and a GC target protein-protein interaction (PPI) network by Cytoscape 3.5.1 and systematically analyzed the potential targets of CKI for the treatment of GC. Finally, molecular docking was applied to verify the key targets. In addition, we analyzed the mechanism of action of the predicted targets by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. RESULTS The results showed that the potential targets, including CCND1, PIK3CA, AKT1, MAPK1, ERBB2, and MMP2, are the therapeutic targets of CKI for the treatment of GC. Functional enrichment analysis indicated that CKI has a therapeutic effect on GC by synergistically regulating some biological pathways, such as the cell cycle, pathways in cancer, the PI3K-AKT signaling pathway, the mTOR signaling pathway, and the FoxO signaling pathway. Moreover, molecular docking simulation indicated that the compounds had good binding activity to PIK3CA, AKT1, MAPK1, ERBB2, and MMP2 in vivo. CONCLUSION This research partially highlighted the molecular mechanism of CKI for the treatment of GC, which has great potential in the identification of the effective compounds in CKI and biomarkers to treat GC.

中文翻译：

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基于网络药理研究复方苦参注射液治疗胃癌的机制。

背景技术尽管很少进行分子机制分析，但复方苦参注射液（CKI）作为胃癌（GC）的有效处方已被广泛使用。方法在本研究中，我们鉴定了16种活性成分和60种GC目标蛋白。然后，我们通过Cytoscape 3.5.1建立了一个化合物预测的目标网络和一个GC目标蛋白-蛋白质相互作用（PPI）网络，并系统分析了CKI治疗GC的潜在目标。最后，应用分子对接验证关键目标。此外，我们通过《京都基因与基因组百科全书》（KEGG）和基因本体论（GO）分析了预测目标的作用机理。结果结果表明，潜在目标包括CCND1，PIK3CA，AKT1，MAPK1，ERBB2和MMP2，是CKI治疗GC的治疗目标。功能富集分析表明，CKI通过协同调节某些生物学途径（例如细胞周期，癌症途径，PI3K-AKT信号途径，mTOR信号途径和FoxO信号途径）对GC具有治疗作用。此外，分子对接模拟表明该化合物在体内对PIK3CA，AKT1，MAPK1，ERBB2和MMP2具有良好的结合活性。结论本研究部分强调了CKI治疗GC的分子机制，在鉴定CKI有效成分和治疗GC的生物标志物方面具有巨大潜力。例如细胞周期，癌症通路，PI3K-AKT信号通路，mTOR信号通路和FoxO信号通路。此外，分子对接模拟表明该化合物在体内对PIK3CA，AKT1，MAPK1，ERBB2和MMP2具有良好的结合活性。结论本研究部分强调了CKI治疗GC的分子机制，在鉴定CKI有效成分和治疗GC的生物标志物方面具有巨大潜力。例如细胞周期，癌症通路，PI3K-AKT信号通路，mTOR信号通路和FoxO信号通路。此外，分子对接模拟表明该化合物在体内对PIK3CA，AKT1，MAPK1，ERBB2和MMP2具有良好的结合活性。结论本研究部分强调了CKI治疗GC的分子机制，在鉴定CKI有效成分和治疗GC的生物标志物方面具有巨大潜力。