Lin Zehua, Huang Ting, Han Baoai, Tao Zezhang, Chen Xiong
Department of Otolaryngology, Head and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China.
Department of Otolaryngology, Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, 430071, Hubei, China.
J Cancer. 2025 Mar 29;16(7):2212-2232. doi: 10.7150/jca.109758. eCollection 2025.
Yi-Yi-Fu-Zi-Bai-Jiang-San (YYFZBJS) is a representative traditional Chinese medicine (TCM) formula. However, its potential anti-tumor effects in nasopharyngeal carcinoma (NPC) remains unclear. This study aims to investigate the monomers of YYFZBJS and their associated targets in the treatment of NPC. The primary active compounds of YYFZBJS and their corresponding targets were identified using the TCMSP, SEA, and Super-PRED databases. NPC-related target proteins were retrieved from OMIM, GeneCards, and TTD databases. A protein-protein interaction network was constructed using the common target proteins of YYFZBJS active compounds and NPC. Core genes were identified through three algorithms in CentiScape 2.2. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were then performed on these core genes. Validation was conducted using the GSE53819 and GSE13597 datasets. Finally, interactions between core targets and active ingredients were confirmed through molecular docking, molecular dynamics simulations, and cell-based experiments. A total of 715 corresponding to YYFZBJS active compounds and 3159 NPC-related targets were screened. Among these, 143 intersection genes were identified, from which 32 core genes were selected based on degree centrality, closeness centrality, and betweenness centrality. GO and KEGG analyses of these core genes revealed relevant biological processes and pathways. Furthermore, these 32 core genes were cross-referenced with the GSE53819 and GSE13597 datasets, identifying PTGS2 and CCND1 as valid targets of active compounds. Molecular docking, molecular dynamics simulations and cell experiments confirmed the effectiveness of the Acacetin-PTGS2 pathway. Acacetin of the main active ingredient in YYFZBJS suppressed NPC by downregulating PTGS2 expression.
抑抑附子败酱散（YYFZBJS）是一种具有代表性的中药方剂。然而，其在鼻咽癌（NPC）中的潜在抗肿瘤作用仍不清楚。本研究旨在探讨YYFZBJS的单体成分及其在NPC治疗中的相关靶点。利用中药系统药理学数据库与分析平台（TCMSP）、SEA数据库和Super-PRED数据库鉴定了YYFZBJS的主要活性成分及其相应靶点。从在线人类孟德尔遗传数据库（OMIM）、基因卡片数据库（GeneCards）和治疗靶点数据库（TTD）中检索NPC相关的靶蛋白。利用YYFZBJS活性成分与NPC的共同靶蛋白构建蛋白质-蛋白质相互作用网络。通过CentiScape 2.2中的三种算法鉴定核心基因。然后对这些核心基因进行基因本体（GO）和京都基因与基因组百科全书（KEGG）分析。使用GSE53819和GSE13597数据集进行验证。最后，通过分子对接、分子动力学模拟和细胞实验证实了核心靶点与活性成分之间的相互作用。共筛选出与YYFZBJS活性成分相对应的715个靶点和3159个NPC相关靶点。其中，鉴定出143个交集基因，并根据度中心性、紧密中心性和中介中心性从中选择了32个核心基因。对这些核心基因的GO和KEGG分析揭示了相关的生物学过程和信号通路。此外，将这32个核心基因与GSE53819和GSE13597数据集进行交叉参考，确定环氧化酶-2（PTGS2）和细胞周期蛋白D1（CCND1）为活性成分的有效靶点。分子对接、分子动力学模拟和细胞实验证实了芹菜素-PTGS2信号通路的有效性。YYFZBJS中的主要活性成分芹菜素通过下调PTGS2表达抑制NPC。
