中国药理学通报2024，Vol.40Issue(1)：146-154,9.DOI:10.12360/CPB202304059
基于网络药理学探讨山奈酚-7-O-新橘皮糖苷抗前列腺癌的作用机制
A network pharmacology-based approach to explore mechanism of kaempferol-7-O-neohesperidoside against prostate cancer
摘要
Abstract
Aim To explore the effect of kaempferol-7-O-neohesperidoside(K7 ON)against prostate cancer(PCa)and the underlying mechanism.Methods The effect of K7ON on the proliferation of PCa cell lines PC3,DU145,C4-2 and LNCaP was detected using CCK8 assay.The effect of K7ON on migration ability of DU145 cells was determined by wound healing as-say.The targets of K7ON and PCa were screened from SuperPred and other databases.The common targets both related to K7ON and PCa were obtained from the Venny online platform;a protein-protein interaction network(PPI)was constructed by the String and Cyto-scape.Meanwhile,the GO and KEGG functional en-richment were analyzed by David database.Then,a"drug-target-disease-pathway"network model was con-structed.Cell cycle of PCa cells treated with K7ON was analyzed by flow cytometry.The expressions of cy-cle-associated proteins including Skp2,p27 and p21 protein were detected by Western blot.Molecular doc-king between Skp2 and K7ON was conducted by Sybyl X2.O.Results K7ON significantly inhibited the pro-liferation and migration of PCa cells.A total number of 34 drug-disease intersection targets were screened.The String results showed that Skp2 and p27,among the common targets,were the key targets of K7 ON for PCa treatment.Furthermore,GO and KEGG functional en-richment indicated that the mechanism was mainly re-lated to the cell cycle.Flow cytometry showed that K7ON treatment induced cell cycle arrest at the S phase.Compared with the control group,the protein expression level of Skp2 was significantly down-regula-ted,while the protein expression levels of p27 and p21 were up-regulated.The network molecular docking in-dicated that the ligand K7 ON had a good binding abili-ty with the receptor Skp2.Conclusions K7ON could inhibit the proliferation and migration of PCa cells,block the cell cycle in the S phase,which may be re-lated to the regulation of cell cycle through the Skp2-p27/p21 signaling pathway.关键词
山奈酚-7-O-新橘皮糖苷/前列腺癌/网络药理学/增殖/迁移/细胞周期/Skp2-p27/p21Key words
kaempferol-7-O-neohesperidoside/pros-tate cancer/network pharmacology/proliferation/mi-gration/cell cycle/Skp2-p27/p21分类
医药卫生引用本文复制引用
张秋萍,付杰军,程智萍,薛薇,李巧凤,郭宏伟..基于网络药理学探讨山奈酚-7-O-新橘皮糖苷抗前列腺癌的作用机制[J].中国药理学通报,2024,40(1):146-154,9.基金项目
广西自然科学基金(No 2023GXNSFDA026047) （No 2023GXNSFDA026047）
国家自然科学基金(No 81660681 （）
82160948) （）
广西医科大学高水平创新团队及杏湖学者计划 （）
