基于网络药理学及分子对接探讨大黄酸治疗结肠癌的潜在机制

Mechanism of Rhein in Treatment of Colon Cancer Based on Network Pharmacology and Molecular Docking Method

目的:通过网络药理学结合分子对接技术研究大黄酸治疗结肠癌的潜在机制。方法:利用中药系统药理学数据库分析网站筛选出大黄酸的潜在作用靶点,在疾病数据库中筛查出结肠癌的相关靶点,将两者取交集得到大黄酸治疗结肠癌的相关靶点;使用蛋白分析数据平台对获得的靶点进行蛋白互作分析,构建相互作用网络;利用DAVID数据库对获得的靶点基因进行GO功能分析及KEGG通路分析;通过分子对接,研究大黄酸与关键靶点的结合机制。结果:大黄酸具有41个治疗结肠癌的相关靶点,并根据蛋白互作网络筛选出Akt1、HSP90AA1、EGFR、KDR、ESR1等多个核心靶点,这些靶点主要富集的通路有脂质和动脉粥样硬化、癌症的通路、雌激素信号通路、MAPK信号通路、PI3K-Akt信号通路等信号通路。通过分子对接发现,大黄酸与关键靶点之间的亲和能均低于-5.0 kcal/mol,表明大黄酸与这些靶点均有较好的结合活性。结论:基于网络药理学和分子对接技术筛选出大黄酸治疗结肠癌的核心靶点基因和主要信号通路,为进一步开展大黄酸抗肿瘤作用研究提供了新思路。

Objective:To explore the mechanism of rhein in the treatment of colon cancer was studied by combining network pharmacology with molecular docking.Methods:Using the traditional Chinese medicine system pharmacology database analysis website to screen potential targets of rhein,screening relevant targets of colon cancer in the disease database,and taking the intersection of the two to obtain relevant targets of rhein for treating colon cancer;The protein analysis data platform was used to analyze the protein interaction of the obtained targets and construct the interaction network.The GO and KEGG pathways involved in the targets were analyzed by using DAVID database.The binding mechanism of rhein to key targets was studied through molecular docking.Results:The results showed that rhein had 41 relevant targets for the treatment of colon cancer,and multiple core targets such as Akt1,HSP90AA1,EGFR,KDR,and ESR1 were screened according to the protein-protein interaction network,and these targets were mainly enriched in lipid and atherosclerosis,cancer pathways,estrogen signaling pathways,MAPK signaling pathways,PI3K-Akt signaling pathways,and other signaling pathways.Through molecular docking,it was found that the affinity between rhein and key targets was lower than-5.0 kcal/mol,indicating that rhein has good binding activity with these targets.Conclusion:Based on network pharmacology and molecular docking technology,the core target genes and main signaling pathways of rhein in the treatment of colon cancer have been screened,providing new ideas for further research on the anti-tumor effect of rhein.