基于网络药理学的复方苦参注射液治疗胃癌作用机制研究。

Study on the mechanisms of compound Kushen injection for the treatment of gastric cancer based on network pharmacology.

机构信息

Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, No. 11 of North Three-ring East Road, Chao Yang District, Beijing, China.

出版信息

BMC Complement Med Ther. 2020 Jan 15;20(1):6. doi: 10.1186/s12906-019-2787-y.

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.

背景

复方苦参注射液（CKI）作为一种有效的胃癌（GC）治疗处方，尽管很少进行分子机制分析，但已被广泛应用。

方法

在本研究中，我们鉴定了 16 种活性成分和 60 个 GC 靶标蛋白。然后，我们通过 Cytoscape 3.5.1 构建了一个化合物-预测靶标网络和一个 GC 靶标蛋白-蛋白相互作用（PPI）网络，并系统分析了 CKI 治疗 GC 的潜在靶标。最后，应用分子对接验证关键靶标。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，对预测靶标的作用机制进行了分析。

结果

结果表明，包括 CCND1、PIK3CA、AKT1、MAPK1、ERBB2 和 MMP2 在内的潜在靶标是 CKI 治疗 GC 的治疗靶标。功能富集分析表明，CKI 通过协同调节细胞周期、癌症途径、PI3K-AKT 信号通路、mTOR 信号通路和 FoxO 信号通路等一些生物学途径对 GC 具有治疗作用。此外，分子对接模拟表明，这些化合物在体内与 PIK3CA、AKT1、MAPK1、ERBB2 和 MMP2 具有良好的结合活性。