betway必威登陆网址 (betway.com )学报››2024,Vol. 45››Issue (1): 7-12.DOI:10.3969/j.issn.2097-0005.2024.01.002

• 基础研究 •上一篇下一篇

异鼠李素对人卵巢癌作用机制

孙同同1, 张栋栋2, 张堃2, 王海静2, 徐蕾2()

  1. 1.betway必威登陆网址 (betway.com )研究生院,山东 济南 250117
    2.淄博市妇幼保健院妇科,山东 淄博 255000
  • 收稿日期:2023-12-14出版日期:2024-01-25发布日期:2024-04-08
  • 通讯作者:徐蕾

The mechanism of action of isorhamnetin on human ovarian cancer

Tongtong SUN1, Dongdong ZHANG2, Kun ZHANG2, Haijing WANG2, Lei XU2()

  1. 1.Graduate School of Shandong First Medical University & Shandong Academy of Medical Sciences,Jinan 250117,China
    2.Zibo Maternal And Child Health Hospital gynaecology,Zibo 255000,China
  • Received:2023-12-14Online:2024-01-25Published:2024-04-08
  • Contact:Lei XU

摘要:

目的基于网络药理学和细胞实验探求异鼠李素治疗卵巢癌的作用机制。方法文献检索收集异鼠李素的作用靶点,通过Swiss Target Prediction数据库预测靶点,下载疾病基因及找到药物及与疾病靶点的交集,进行蛋白质-蛋白质相互作用分析,用Cytoscape软件得到核心基因,进行富集分析及分子对接。体外培养人卵巢癌SKOV3细胞,用不同浓度的异鼠李素(0、10、25 mg/L)处理细胞,比较各组细胞抑制率,并进行AKT、p-AKT、Bcl2、BAX蛋白表达比较。结果异鼠李素作用于卵巢癌的96个潜在靶点及14个核心基因。富集分析结果提示,作用靶点与丝氨酸/苏氨酸蛋白激酶有关,主要富集在PI3K/AKT通路,分子对接提示异鼠李素与各靶点具有良好的结合活性。体外实验证实异鼠李素可以抑制卵巢癌细胞的活性,流式细胞检测发现异鼠李素处理组凋亡率增加,Western blot结果显示,异鼠李素可以降低p-AKT/AKT蛋白表达比率、降低Bcl2及升高BAX蛋白的表达,从而发挥抗肿瘤作用。结论异鼠李素可以促进卵巢癌细胞的凋亡。

关键词:异鼠李素,卵巢癌,网络药理学,机制

Abstract:

ObjectiveTo explore the mechanism of isorhamnetin in the treatment of ovarian cancer based on network pharmacology and cell experiments.MethodsThe targets of isorhamnetin were collected by literature retrieval; to use Swiss Target Prediction to predict targets, to downloaded disease genes and find the intersection of drug and disease targets, and to perform protein-protein interaction (PPI) analysis. The core genes were obtained by Cytoscape, and enrichment analysis and molecular docking were performed. Human ovarian cancer SKOV3 cells were cultured in vitro, and treated with different concentrations of isorhamnetin (0, 10, 25) mg/L to compare the cell inhibition rate of each group, and the protein expressions of AKT, p-AKT, Bcl2 and BAX were compared.Results96 potential targets and 14 core genes of isorhamnetin were found in ovarian cancer. The results of enrichment analysis suggested that the targets were related to serine/threonine protein kinase, mainly enriched in the PI3K/AKT pathway, and the molecular docking suggested that isorhamnetin had good binding activity with each target. The In vitro experiments confirmed that isorhamnetin could inhibit the activity of ovarian cancer cells. Flow cytometry detection found that the apoptosis rate of isorhamnetin treatment group increased. The results of Western blot showed that isorhamnetin could reduce the p-AKT/AKT protein expression ratio, reduce Bcl2 and increase BAX protein expression, thereby exerting anti-tumor effect.ConclusionIsophoronin can promote the apoptosis of ovarian cancer cells.

Key words:isorhamnetin,ovarian cancer,network pharmacology,mechanism