基于网络药理学、生物信息学及分子对接探究红景天苷治疗肾癌作用及机制

Exploration of the Therapeutic Effect and Mechanism of Salidroside on Renal Cell Carcinoma Based on Network Pharmacology, Bioinformatics and Molecular Docking

摘要: 肾癌是泌尿系统常见的恶性肿瘤，对传统治疗手段效果有限。红景天苷具有显著的抗肿瘤作用，能够通过多种途径抑制肿瘤的增殖、迁移、转移，促进肿瘤细胞的凋亡，然而其对肾癌的作用及机制鲜有研究。本研究通过网络药理学、生物信息学和分子对接，整合红景天苷和肾癌相关靶点，进一步分析红景天苷治疗肾癌的潜在作用靶点和通路。研究结果显示，红景天苷与肾癌共存在222个交集靶点，基因本体(Gene Ontology, GO)富集分析主要与蛋白质磷酸化、细胞质、细胞外外泌体、组蛋白H2AXY142激酶活性等569个条目相关；京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes, KEGG)通路富集分析主要包括癌症通路和代谢通路等；通过STRING构建蛋白互作网络，Cytoscape软件筛选核心靶点，排名前5位的核心靶点为EGFR、CASP3、AKT1、GAPDH和SRC；生存分析结果显示GAPDH和SRC的高表达与肾癌患者的较短生存期显著相关，而AKT1的高表达则与肾癌患者的较长生存期显著相关；分子对接结果显示，前5位核心靶点均能与红景天苷自发结合。研究表明，红景天苷通过调节GAPDH、SRC、AKT1等核心靶点的表达抑制肾癌，涉及的主要通路为癌症通路和代谢通路等。

Abstract: Renal cell carcinoma (RCC) is a common malignant tumor in the urinary system, and it shows limited response to traditional treatment methods. Salidroside has significant anti-tumor effects, which can inhibit the proliferation, migration, and metastasis of tumors and promote the apoptosis of tumor cells through multiple pathways. However, there are few studies on the effects and mechanisms of salidroside on RCC. This study integrates salidroside and RCC-related targets through network pharmacology, bioinformatics, and molecular docking to further analyze the potential targets and pathways of. The results showed that salidroside shared 222 intersection targets with RCC. Gene Ontology (GO) enrichment analysis was mainly related to protein phosphorylation, cytoplasm, extracellular exosomes, histone H2AXY142 kinase activity, etc., with 569 entries; Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis mainly included pathways in cancer and metabolic pathways, etc. The protein interaction network was constructed by STRING, and the hub genes were screened by Cytoscape software. The top 5 hub genes were EGFR, CASP3, AKT1, GAPDH, and SRC. The survival analysis showed that high expression of GAPDH and SRC was significantly associated with shorter survival periods of RCC patients, while high expression of AKT1 was significantly associated with longer survival periods. The molecular docking results showed that all the top 5 hub genes spontaneously bound to salidroside. The study indicated that salidroside inhibited RCC by regulating the expression of hub genes such as GAPDH, SRC, and AKT1, involving main pathways such as the pathway in cancer and the metabolic pathway.