Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland).
Shandong Key Laboratory of Digital Medicine and Computer Assisted Surgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland).
Med Sci Monit. 2020 Apr 4;26:e921162. doi: 10.12659/MSM.921162.
BACKGROUND This study used network pharmacology method and cell model to assess the effects of Radix Astragali (RA) on cholangiocarcinoma (CCA) and to predict core targets and molecular mechanisms. MATERIAL AND METHODS We performed an in vitro study to assess the effect of RA on CCA using CCK8 assay, the Live-Cell Analysis System, and trypan blue staining. The components and targets of RA were analyzed using the Traditional Chinese Medicine Systems Pharmacology database, and genes associated with CCA were retrieved from the GeneCards and OMIM platforms. Protein-protein interactions were analyzed with the STRING platform. The components-targets-disease network was built by Cytoscape. The TIMER database revealed the expression of core targets with diverse immune infiltration levels. GO and KEGG analyses were performed to identify molecular-biology processes and signaling pathways. The predictions were verified by Western blotting. RESULTS Concentration-dependent antitumor activity was confirmed in the cholangiocarcinoma QBC939 cell line treated with RA. RA contained 16 active compounds, with quercetin and kaempferol as the core compounds. The most important biotargets for RA in CCA were caspase 3, MAPK8, MYC, EGFR, and PARP. The TIMER database revealed that the expression of caspase3 and MYC was related with diverse immune infiltration levels of CCA. The results of Western blotting showed RA significantly influenced the expression of the 5 targets that network pharmacology predicted. CONCLUSIONS RA is an active medicinal material that can be developed into a safe and effective multi-targeted anticancer treatment for CCA.
本研究采用网络药理学方法和细胞模型，评估黄芪（RA）对胆管癌（CCA）的作用，并预测核心靶点和分子机制。
我们进行了一项体外研究，使用 CCK8 测定法、活细胞分析系统和台盼蓝染色法评估 RA 对 CCA 的作用。使用中药系统药理学数据库分析 RA 的成分和靶点，并从 GeneCards 和 OMIM 平台检索与 CCA 相关的基因。使用 STRING 平台分析蛋白质-蛋白质相互作用。通过 Cytoscape 构建成分-靶点-疾病网络。TIMER 数据库揭示了具有不同免疫浸润水平的核心靶标的表达。进行 GO 和 KEGG 分析以确定分子生物学过程和信号通路。通过 Western blot 验证预测。
在 RA 处理的胆管癌细胞系 QBC939 中，证实了浓度依赖性的抗肿瘤活性。RA 含有 16 种活性化合物，槲皮素和山奈酚是其核心化合物。RA 在 CCA 中的最重要的生物靶标是 caspase3、MAPK8、MYC、EGFR 和 PARP。TIMER 数据库显示 caspase3 和 MYC 的表达与 CCA 的不同免疫浸润水平有关。Western blot 结果表明，RA 显著影响网络药理学预测的 5 个靶标的表达。
RA 是一种活性药材，可开发为安全有效的 CCA 多靶点抗癌治疗药物。
