紫檀芪调控KDR和EGFR活性发挥抗肾细胞癌作用研究

Pterostilbene inhibits renal cell carcinoma by regulating the activity of KDR and EGFR

目的利用网络药理学对紫檀芪抗肾细胞癌潜在靶点进行预测,探讨其多靶点、多通路机制抗肾透明细胞癌的分子机制。方法利用TCMSP、Swiss Target Prediction、Chembl数据库预测紫檀芪的作用靶点,利用OMIM、DisGeNET数据库获得肾细胞癌相关靶点蛋白,对两者靶点进行交集,并用JVENN绘制Venn图,利用STRING及Cytoscape构建PPI网络,根据degree值筛选出关键蛋白,利用GEPIA数据库分析关键蛋白在肾癌细胞及配对正常肾细胞中的差异表达,并利用分子对接对紫檀芪与关键蛋白相关作用进行验证。结果紫檀芪的潜在靶点有614个,肾透明细胞癌的相关靶点有280个,两者共同作用的靶点有33个,关键的靶点包括MAPK1、EGFR、AKT1、PIK3CB、KDR,其中KDR和EGFR在肾细胞癌中表达显著高于正常配对的肾组织。分子对接发现紫檀芪与KDR和EGFR均具有较好的结合能力。结论紫檀芪抗肾细胞癌具有多靶点、多途径的特点,KDR和EGFR可能为紫檀芪抗肾细胞癌的关键靶点。

Objective To predict the potential targets of pterostilbene against renal cell carcinoma(RCC) based on network pharmacology. Methods The targets of pterostilbene was collected by TCMSP, Swiss Target Prediction and Chembl databases, and RCC associated targets was obtained by using DisGeNET and OMIM databases. The two targets were intersected and the Venn diagram was drawn by using JVENN sofeware. The PPI network of targets of pterostilbene against RCC was constructed by STRING and Cytoscape. The key targets were screened according to the degree value.GEPIA database was used to analyze the differential expression of key proteins in renal cancer cells and paired normal renal cells, and molecular docking was used to verify the relationship between pterostilbene and key proteins. Results There were 614 potential targets of pterostilbene, 280 RCC related targets and 33 potential targets of pterostilbene against RCC. The key targets included MAPK1, EGFR, AKT1, PIK3 CB and KDR. The expression of KDR and EGFR in RCCwere all significantly higher than that in normal paired renal tissue. Molecular docking showed that pterostilbene had bettter binding ability with KDR and EGFR. Conclusion Pterostilbene has the characteristics of multiple targets and pathways in the treatment of RCC. KDR and EGFR may be the key targets of pterostilbeneagainst RCC.