文献类型：期刊文献

中文题名：基于网络药理学、分子对接及实验验证探讨参芪抑瘤方治疗卵巢癌作用机制

英文题名：Exploration on the Mechanism of Shenqi Yiliu Prescription for Ovarian Cancer Based on Network Pharmacology,Molecular Docking and Experimental Validation

作者：马兰[1];杨玉萍[2];白敏[3];张治宁[1];段永强[3]

第一作者：马兰

机构：[1]宁夏医科大学总医院,宁夏银川750004;[2]甘肃中医药大学中医临床学院,甘肃兰州730000;[3]宁夏医科大学宁夏少数民族医药现代化教育部重点实验室,宁夏银川750004

第一机构：宁夏医科大学总医院,宁夏银川750004

年份：2025

卷号：32

期号：7

起止页码：42

中文期刊名：中国中医药信息杂志

外文期刊名：Chinese Journal of Information on Traditional Chinese Medicine

基金：宁夏医科大学校级科研项目(XM2022042)。

语种：中文

中文关键词：卵巢癌;参芪抑瘤方;网络药理学;分子对接;AKT-MDM2-P53信号通路

外文关键词：ovarian cancer;Shenqi Yiliu Prescription;network pharmacology;molecular docking;AKT-MDM2-P53 signaling pathway

摘要：目的基于网络药理学和分子对接技术预测参芪抑瘤方治疗卵巢癌的分子机制,并进行实验验证。方法通过TCMSP数据库检索并筛选参芪抑瘤方药物有效成分及其对应靶点,通过GeneCards数据库查找卵巢癌疾病靶点,利用STRING数据库建立药物与疾病交集靶点蛋白相互作用网络,并进行GO和KEGG通路富集分析,将关键活性成分与核心靶点进行分子对接。采用低、中、高剂量参芪抑瘤方含药血清干预卵巢癌A2780细胞,ELISA检测细胞上清液肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-17含量,TUNEL染色检测细胞凋亡,Western blot检测磷酸化磷脂酰肌醇3激酶(p-PI3K)、磷酸化蛋白激酶B(p-AKT)、磷酸化T218(MDM2)、肿瘤蛋白P53(P53)蛋白表达,实时荧光定量PCR检测PI3K、AKT、MDM2、P53 mRNA表达。结果网络药理学分析表明,槲皮素、β-谷甾醇、山柰酚是参芪抑瘤方治疗卵巢癌的主要活性成分,TP53、AKT1、TNF是核心靶点,分子对接结果显示,关键活性成分与核心靶点均能较好结合,KEGG通路富集分析显示,PI3K/AKT信号通路可能是参芪抑瘤方干预卵巢癌的核心通路。细胞实验结果表明,与对照组比较,参芪抑瘤方各剂量组细胞上清液TNF-α、IL-17含量降低(P<0.05),细胞凋亡率升高(P<0.05),p-PI3K、p-AKT、MDM2蛋白及PI3K、AKT、MDM2、P53 mRNA表达降低(P<0.05),P53蛋白及mRNA表达降低(P<0.05),且参芪抑瘤方干预效果具有剂量依赖性。结论参芪抑瘤方能有效抑制卵巢癌细胞增殖并促进其凋亡,其作用机制可能与抑制AKT-MDM2-P53信号通路活化,降低IL-17、TNF-α含量有关。
Objective To predict the molecular mechanism of Shenqi Yiliu Prescription for the treatment of ovarian cancer based on network pharmacology and molecular docking technology;To conduct experimental validation.Methods The active components and targets of Shenqi Yiliu Prescription were retrieved and screened through TCMSP database,and ovarian cancer disease targets were searched through GeneCards database.A protein-protein interaction network between drugs and disease was established using the STRING database,and GO and KEGG pathway enrichment analysis was performed.Molecular docking between key active components and core targets was conducted.Ovarian cancer A2780 cells were intervened with Shenqi Yiliu Prescription low-,medium-and high-dosages containing serum.ELISA was used to detect TNF-αand IL-17 contents in cell supernatant;TUNEL staining was used to detect cell apoptosis;Western blot was used to detect the protein expressions of p-PI3K,p-AKT,phosphorylated T218(MDM2),and tumor protein P53(P53);real-time fluorescence quantitative PCR was used to detect the mRNA expressions of PI3K,AKT,MDM2 and P53.Results Network pharmacology analysis showed that quercetin,β-sitosterol and kaempferol were the active components of Shenqi Yiliu Prescription to treat ovarian cancer,and TP53,AKT1 and TNF were the core targets.The molecular docking results showed that the key active components could bind well to the core targets.KEGG enrichment analysis showed that the PI3K/AKT signaling pathway may be the core pathway for Shenqi Yiliu Prescription to intervene in ovarian cancer.The cell experiment results showed that compared with the control group,the contents of TNF-αand IL-17 in cell supernatant decreased(P<0.05),the apoptosis rate increased(P<0.05),the expressions of p-PI3K,p-AKT,MDM2 protein and PI3K,AKT,MDM2 mRNA decreased(P<0.05),and the expressions of P53 protein and mRNA decreased(P<0.05)in each Shenqi Yiliu Prescription group.Moreover,the intervention effect of Shenqi Yiliu Prescription was dose-dependent.Conclusion Shenqi Yiliu Prescription can effectively inhibit the proliferation and promote apoptosis of ovarian cancer cells,and its possible mechanism maybe related to inhibition of the activation of AKT-MDM2-P53 signaling pathway and the reduction of IL-17 and TNF-αcontents.