基于网络药理学探讨小柴胡汤增强鼻咽癌放疗敏感性的分子机制

Molecular mechanism of small bupleurum decoction in enhancing radiosensitivity of nasopharynx cancer based on network pharmacology

目的探讨小柴胡汤增强鼻咽癌(NPC)放疗敏感性的分子机制。方法通过中药系统药理学分析平台(TCMSP)筛选小柴胡汤的活性成分及靶点;检索GEO数据库获取鼻咽癌放疗抵抗差异性表达基因;采用交集法获得小柴胡汤与鼻咽癌放疗抵抗的相关靶点,并对交集靶点进行网络拓扑分析、GO和KEGG富集分析。结果发现小柴胡汤改善放疗抵抗的潜在靶点38个;小柴胡汤改善鼻咽癌放疗抵抗的活性成分主要为槲皮素、山奈酚、芒柄花黄素;出现频次较高的靶点有MAPK3、CAT、CASP3、PPARG和CCND1,这些靶点富集在化学癌变-受体的激活、p53信号通路、凋亡等信号通路,参与药物反应、氧化应激、有毒物质反应、RNA聚合酶调控、细胞黏附等过程。结论小柴胡汤可通过多成分、多靶点、多途径的方式增强鼻咽癌放疗敏感性,进而为其临床应用提供了新的理论依据。

Objective To investigate the molecular mechanism of small bupleurum decoction in enhancing radiosensitivity of nasopharynx cancer.Methods The active components and targets of small bupleurum decoction were screened by Traditional Chinese Medicine System Pharmacology(TCMSP),and the differentially expressed genes of nasopharyngeal carcinoma radioresistance were obtained from GEO database.The related targets of small bupleurum decoction and nasopharyngeal carcinoma radioresistance were obtained by intersection method,and network topological analysis,GO and KEGG enrichment analysis were performed on the intersection targets.Results 38 potential targets of small bupleurum decoction in improving radioresistance were found,and the active components of small bupleurum decoction in improving radioresistance of nasopharynx cancer mainly were quercetin,kaempferol,and formononetin.Targets with high frequency were MAPK3,CAT,CASP3,PPARG,and CCND1,which were enriched in pathways of chemical carcinogenesis-receptor activation,p53,and apoptosis,etc.and participated in processes of drug reaction,oxidative stress,toxic substance reaction,RNA polymerase regulation,and cell adhesion,etc.Conclusion Small bupleurum decoction can enhance the radiosensitivity of nasopharynx cancer through multiple components,multiple targets and multiple pathways,which provides a new theoretical basis for its clinical application.