基于网络药理学探讨原花青素A2抗前列腺癌的作用机制  

Exploring the Mechanism of Anti Prostate Cancer Effect of Proanthocyanidin A2 Based on Network Pharmacology

作　　者：常秀亭 陈琳琳 蔡家蕙 寇力丹 罗小菊 王彬 Chang Xiuting;Chen Linlin;Cai Jiahui;Kou Lidan;Luo Xiaoju;Wang Bin(Hainan Academy of Inspection and Testing,Key Laboratory of Tropical Fruits and Vegetables Quality and Safety for State Market Regulation,Haikou 570314,China;School of Pharmaceutical Sciences,Hainan University,Haikou 570228,China;Yuebei People′s Hospital Affiliated to Medical College of Shantou University,Shaoguan 512026,China;Clinical Biobank,Beijing Hospital,National Center of Gerontology,National Health Commission,Institute of Geriatric Medicine,Chinese Academy of Medical Sciences,Beijing 100005,China)

机构地区：[1]海南省检验检测研究院,国家市场监管重点实验室<热带果蔬质量与安全>,海口570314 [2]海南大学,海口570228 [3]汕头大学医学院附属粤北人民医院,韶关512026 [4]北京医院临床生物样本管理中心,国家老年医学中心中国医学科学院老年医学研究院,北京100005

出　　处：《中国药事》2024年第12期1429-1437,共9页Chinese Pharmaceutical Affairs

基　　金：海南省自然科学基金面上项目(编号823MS135);国家市场监管重点实验室(热带果蔬质量与安全)课题资助项目(编号ZZ-2023012)。

摘　　要：目的:基于网络药理学和体外细胞实验探讨原花青素A2(Proanthocyanidin A2,PCA2)对人前列腺癌细胞系(PC-3细胞)增殖和迁移能力的作用及其抗癌潜在的分子机制。方法:采用CCK8实验检测不同浓度PCA2对PC-3细胞的细胞增殖的影响,克隆形成实验和划痕实验检测PCA2对PC-3细胞增殖与迁移的影响。通过Similarity Ensemble Approach等数据库获取PCA2和前列腺癌的预测靶点,应用String构建蛋白相互作用网络,根据OmicShare Tools数据库进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析以预测其作用机制。结果与结论:研究发现PCA2能显著抑制PC-3细胞的增殖和迁移,且抑制作用与PCA2浓度呈正相关。并使用网络药理学方法筛选出PCA2与前列腺癌疾病的交集靶点共95个,其中EGFR、ALB、HSP90AA1和MMP9等是PCA2抗前列腺癌的核心靶点。GO和KEGG富集分析发现其相关的主要机制与磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/AKT)信号通路有关。Objective:To investigate the effects of proanthocyanidin A2(PCA2)on the proliferation and migration of human prostate cancer cells(PC-3 cells)by cytological tests in vitro,and to elucidate its potential anti-cancer molecular mechanisms based on network pharmacology.Methods:The effects of varying concentrations of PCA2 on PC-3 cell proliferation were assessed using CCK8 assay.Colony formation and scratch assays were used to determine the effects of PCA2 on PC-3 cell proliferation and migration.Predicted targets of PCA2 and prostate cancer were identified through Similarity Ensemble Approach and other databases,and a protein-protein interaction network was constructed using String.GO and KEGG functional enrichment analyses were performed using the OmicShare Tools database to predict the mechanisms of action.Results and Conclusion:PCA2 significantly inhibited the proliferation and migration of PC-3 cells,and the inhibitory effect is positively correlated with the concentration of PCA2.Through network pharmacology,95 targets were identified between PCA2 and prostate cancer,with EGFR,ALB,HSP90AA1,and MMP9 being the core targets.GO and KEGG functional enrichment analyses indicated that its main mechanism related to the PI3K/AKT signaling pathway.

关 键 词：原花青素A2 前列腺癌 人前列腺癌细胞系 迁移增殖 PI3K/AKT信号通路 

分 类 号：R932[医药卫生—生药学]