【摘要】 目的 通过网络药理学和分子对接技术探究姜黄素治疗骨肉瘤的作用机制。方法 采用PharmMapper数据库筛选姜黄素的潜在作用靶点,采用GeneCards数据库获得骨肉瘤的相关靶点,通过韦恩图获得姜黄素和骨肉瘤的交集靶点。使用Cytoscape软件构建“化合物-靶点”网络图,应用R语言软件对靶点基因进行基因本体论(GO)功能富集和京都基因组百科全书(KEGG)通路富集分析;筛选核心靶点与其对应的活性成分进行分子对接验证。结果 共获得姜黄素在骨肉瘤治疗中可能作用的靶标基因102个。通过GO功能和KEGG通路富集分析,发现核心通路为丝裂原活化蛋白激酶(MAPK)、磷脂酰肌醇-3-激酶/蛋白激酶(PI3K/Akt)信号通路。分子对接显示,姜黄素与核心通路中多个靶蛋白有较好的结合活性。结论 姜黄素主要通过调节MAPK、PI3K/Akt信号通路来发挥抗骨肉瘤的作用,通过影响INSR、IGF1、KDR、RAC1、EGFR、FGFR1、FGFR2和MET等蛋白来展现其抗骨肉瘤的功效。更多还原

【Abstract】 Objective To explore the mechanism of curcumin in the treatment of osteosarcoma by network pharmacology and molecular docking technology. Methods The potential targets of curcumin were screened by PharmMapper database. The related targets of osteosarcoma were obtained by GeneCards database. The intersection targets of curcumin and osteosarcoma were obtained by Venn diagram. Cytoscape software was used to construct the "Compound Target" network diagram, and R language software was used to analyze the gene ontology(GO) function and Gene Encyclopedia(KEGG) pathway enrichment of target genes. The core target was screened for molecular docking verification with its corresponding active ingredient. Results A total of 102 potential target genes of curcumin that may be involved in the treatment of osteosarcoma were obtained. Through GO function and KEGG pathway enrichment analysis, it was found that the core pathways were mitogen-activated protein kinase(MAPK) and phosphatidylinositol-3-kinase/protein kinase(PI3K/Akt) signaling pathways. Molecular docking showed that curcumin had good binding activity to multiple target proteins in the core pathway. Conclusion Curcumin mainly plays an anti-osteosarcoma role by regulating the MAPK and PI3K-Akt signaling pathways. It demonstrates its anti-osteosarcoma effect by affecting proteins such as INSR, IGF1, KDR, RAC1, EGFR, FGFR1, FGFR2, and MET.更多还原