基于网络药理学方法的左金丸治疗结直肠癌的作用机制分析

Mechanism Analysis of Zuojin Pills’ Efficiency on Colorectal Cancer Based on Network Pharmacology

目的:运用网络药理学方法探究左金丸治疗结直肠癌的潜在效应机制。方法:依托中药系统药理学分析平台收集左金丸中黄连和吴茱萸的化学成分和靶点信息,通过疾病基因库收集结直肠癌疾病基因,并通过维恩分析、蛋白互作分析以及Cytoscape的可视化功能,构建化合物-靶点网络、蛋白互作(PPI)网络和成分-靶点-通路网络,分析左金丸治疗结直肠癌的效应机制。结果:从左金丸化合物-靶点网络得到234种成分和482个核心靶点(其中活性成分36个,核心靶点72个),结直肠癌基因737个,PPI网络包含50个蛋白,其主要蛋白涉及PIK3CA、AKT1、TP53、HIF-1α、BAX和MYC等。基因GO本体条目283条,涉及核质、细胞凋亡、基因表达调控等方面, KEGG通路58条,主要涉及有癌症的途径、癌症中的蛋白多糖、结肠癌、膀胱癌、乙型肝炎,以及HIF-1信号通路、PI3K信号通路和FOXO信号通路等,其结果有待进一步的实验验证。结论:结合文献报道和预测分析,左金丸可能的作用机制与以下相关:①调节机体免疫耐受能力,增强宿主免疫抵抗,抑制炎症对肠粘膜的持续性刺激,进而阻止了细胞的异常增生;②通过上调抑癌基因,下调癌症相关因子,促进肿瘤细胞发生凋亡;③降低肿瘤细胞的耐受缺氧环境,促进细胞细胞发生凋亡及上皮间质的转移。

Objective: To explore the potential mechanism of Zuojin pills in the treatment of colorectal cancer(CRC) using network pharmacology method. Methods: Chemical composition and target information in Rhizoma Coptidis and Fructus Evodiae, composes in Zuojin pills, were collected based on the public pharmacological analysis platform. By venn,protein interaction analysis and cytoscape visualization, the compound-target network, protein-protein interaction(PPI)network and compound-target-pathway network were constructed to explore the effective mechanism of Zuojin pills.Results: A total of 234 compounds and 482 targets(contain 36 active compounds and 72 coretagets) were collected.There were 737 targets in CRC and the 50 targets in PPI network, among the important targets involving PIK3 CA, AKT1,TP53, HIF-1α, BAX and MYC,etc. There were 283 GO terms involving nucleus, cell apoptosis, gene expression regulation etc. and 58 KEGG pathways terms involving cancer signaling pathway, proteoglycans in cancer, colorectal cancer, bladder cancer, Hepatitis B, HIF-1 signaling pathway, PI3 K signaling pathway and FOXO signaling pathway.The results need further experimental verification. Conclusion: Based on the network pharmacology analysis, we predicted that the effective mechanism of Zuojin pills on CRC may be:① enhancing the host immune resistance,inhibition of inflammatory stimulation and protection of the intestinal mucosa, which in turn prevente of cell invasion;②regulating the genes inhibition of tumor vascular permeability and angiogenesis;③ reducing the tumor cells’ tolerance of hypoxic environment and promoting cell apoptosis and epithelial metastasis.