基于网络药理学和分子对接探讨蛇床子治疗乳腺癌的作用机制

doi:10.3976/j.issn.1002-4026.2022.06.007

摘要/Abstract

摘要：

利用网络药理学和分子对接探讨蛇床子抗乳腺癌的分子机制。采用中药系统药理学数据库与分析平台获取中药蛇床子的化学成分及其相关靶点,借助Uniprot数据库进行基因转换;在GeneCards、OMIM数据库中检索乳腺癌疾病的相关靶点;利用Venn在线软件获取药物与疾病的共同靶点;由Cytoscape 3.7.2绘制药物-成分-靶点-疾病网络;STRING数据库构建蛋白质-蛋白质相互作用网络;基于DAVID数据库对靶点进行基因本体功能富集和京都基因与基因组百科全书通路富集分析,运用AutoDock软件对蛇床子的关键活性成分与作用靶点进行分子对接验证。结果表明, 蛇床子的17个有效成分通过调控19个靶点和56条通路对乳腺癌产生作用,4个关键的化合物分别为β-谷甾醇、(E)-2,3-bis(2-keto-7-methoxy-chromen-8-yl)acrolein、豆甾醇、蛇床子素,可通过HSP90AA1、JUN、PRKACA、KDR等关键靶点介导癌症通路、癌症的蛋白聚糖、粘着斑、PI3K-Akt等信号通路发挥抗乳腺癌作用。该研究初步揭示了蛇床子抗乳腺癌的作用机制,为蛇床子的临床应用及其治疗乳腺癌的相关研究提供了理论依据。

关键词: 网络药理学, 分子对接, 蛇床子, 乳腺癌, 作用机制

Abstract:

The study aimed to investigate the potential therapy targets and pharmacological mechanism of Cnidii Fructus for the treatment of breast cancer using network pharmacology and molecular docking. The active components of Cnidii Fructus and the potential targets of active components were obtained via the traditional Chinese medicine systems pharmacology database and analysis platform, and the gene conversions were obtained using the UniProt database. The targets of breast cancer were retrieved from GeneCards and OMIM database. The Venn online software was used to obtain the common targets of drug and disease, and then the drug-compound-target-disease network diagram was constructed using the Cytoscape 3.7.2 software. The STRING database was employed to draw the protein-protein interaction network. Further, the DAVID database was used to perform gene ontology function and Kyoto encyclopedia of genes and genomes pathway enrichment analysis on the effective targets, and the AutoDock software was used to verify the molecular docking of active components and core targets. The results revealed that 17 active components of the Cnidii Fructus regulated 19 targets and 56 pathways to treat breast cancer. The four key compounds were beta-sitosterol, (E)-2,3-bis(2-keto-7-methoxy-chromen-8-yl)acrolein, stigmasterol, and osthol, which generally mediate pathways in cancer, proteoglycans in cancer, focal adhesion, PI3K-Akt, and other signaling pathways. These pathways are mediated via HSP90AA1, JUN, PRKACA, KDR, and other key targets to exert the anti-breast cancer effects. The study preliminarily reveals the molecular mechanism of Cnidii Fructus against breast cancer and provides a theoretical basis for the clinical application of Cnidii Fructus and its related research on breast cancer.

Key words: network pharmacology, molecular docking, Cnidii Fructus, breast cancer, mechanism of action

中图分类号:

R285

柯昌虎, 潘长江, 严慧, 刘佳玲, 陈苗, 李志浩. 基于网络药理学和分子对接探讨蛇床子治疗乳腺癌的作用机制[J]. 山东科学, 2022, 35(6): 50-57.

KE Chang-hu, PAN Chang-jiang, YAN Hui, LIU Jia-ling, CHEN Miao, LI Zhi-hao. Using network pharmacology and molecular docking to determine the mechanism of Cnidii Fructus in the treatment of breast cancer[J]. Shandong Science, 2022, 35(6): 50-57.

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编号	Mol ID	活性成分	中文名	OB/%	DL
1	MOL000449	Stigmasterol	豆甾醇	43.83	0.76
2	MOL001771	Poriferast-5-en-3beta-ol	穿贝海绵甾醇	36.91	0.75
3	MOL000358	Beta-sitosterol	β-谷甾醇	36.91	0.75
4	MOL001510	24-epicampesterol	22,23-二氢菜子甾醇	37.58	0.71
5	MOL003605	(E)-2,3-bis(2-keto-7-methoxy-chromen-8-yl)acrolein	—	56.38	0.71
6	MOL003591	Ar-curcumene	芳-姜黄烯	52.34	0.65
7	MOL003607	Cniforin B	—	36.70	0.60
8	MOL003606	Cniforin A	O-乙酰异蛇床素	55.89	0.47
9	MOL003624	O-Isovalerylcolum bianetin	邻-异戊酰基二氢山芹醇	64.03	0.36
10	MOL003604	Cnidimol F	—	54.43	0.28
11	MOL002881	Diosmetin	香叶木素	31.14	0.27
12	MOL003600	Cnidimol B	—	68.66	0.26
13	MOL003608	O-Acetylcolumbianetin	O-乙酰二氢欧山芹酯	60.04	0.26
14	MOL003617	Isogosferol	异栓翅芹醇	30.07	0.25
15	MOL003626	Ostruthin	欧芹素	30.65	0.23
16	MOL001941	Ammidin	欧前胡素	34.55	0.22
17	MOL003588	Prangenidin	别欧前胡素	36.31	0.22
18	MOL003584	Xanthoxylin N	美花椒内酯	35.51	0.21
19	MOL002883	Ethyl oleate (NF)	油酸乙酯	32.40	0.19
20	MOL000614	Osthol	蛇床子素	38.75	0.13

靶点	PDB ID	结合能/(kJ·mol^-1)
靶点	PDB ID	A	B	C	D
HSP90AA1	5NJX	-25.15	-21.67	-25.56	-21.13
JUN	1-jun	-18.95	-16.78	-19.83	-15.86
PRKACA	4021	-27.15	-28.45	-28.74	-21.09
KDR	2P2I	-28.37	-20.88	-28.58	-21.76