| 辛恬熙,褚福浩,李园,等.基于网络药理学和实验验证探究槲皮素治疗乳腺癌转移的作用机制[J].浙江中医药大学学报,2023,47(5):463-472. |
| 基于网络药理学和实验验证探究槲皮素治疗乳腺癌转移的作用机制 |
| Based on Network Pharmacology and Experimental Verification to Explore the Mechanism of Quercetin in the Treatment of Breast Cancer Metastasis |
| DOI：10.16466/j.issn1005-5509.2023.05.002 |
| 中文关键词: 槲皮素 乳腺癌转移 网络药理学 SRC 局灶性黏附 信号通路 |
| 英文关键词: quercetin breast cancer metastasis network pharmacology SRC focal adhesion signaling pathway |
| 基金项目:国家自然科学基金项目(81630080) |
|
| 摘要点击次数: 1727 |
| 全文下载次数: 895 |
| 中文摘要: |
| [目的] 利用网络药理学和实验验证探究槲皮素(quercetin)抑制乳腺癌转移(breast cancer metastasis，BCM)的作用机制。[方法] 通过中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform，TCMSP)和Swiss Target Prediction平台预测槲皮素潜在靶点，利用人类基因数据库(Human Gene Database，GeneCards)和在线人类孟德尔遗传(Online Mendelian Inheritance in Man，OMIM)数据库检索BCM相关的靶点，运用Cytoscape 3.7.0软件构建槲皮素和BCM交集靶点的蛋白互作(protein-protein interaction，PPI)网络，使用R软件和Bioconductor安装包完成基因本体(gene oncology，GO)分析及京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes，KEGG)通路分析，结合分子对接探究槲皮素和通路关键靶蛋白的结合作用。运用噻唑蓝(methyl thiazolyl tetrazolium，MTT)实验、细胞划痕实验、Transwell实验和免疫印迹法探究槲皮素抑制BCM的相关机制。[结果] 槲皮素与BCM共有112个交集靶点，KEGG富集分析提示局灶性黏附(focal adhesion，FAs)是槲皮素治疗BCM的主要通路，分子对接结果表明槲皮素与FAs通路的关键靶点具有较强的结合作用。MTT、划痕实验和Transwell实验提示，槲皮素能明显抑制BCAP-37和4T1细胞的增殖、迁移及侵袭能力(P＜0.05)。免疫印迹实验结果表明，槲皮素抑制FAs通路中肉瘤基因(sarcoma gene，SRC)、局灶黏附激酶(focal adhesion kinase，FAK)和蛋白激酶B(protein kinase B，Akt)的活化程度，降低磷脂酰肌醇-3-激酶(phosphatidylinositol-3-kinase，PI3K)蛋白表达(P＜0.05)。[结论] 槲皮素通过降低SRC/FAK/PI3K信号通路活性，达到抑制BCM的目的。 |
| 英文摘要: |
| [Objective] To explore the mechanism of quercetin inhibiting breast cancer metastasis(BCM) by network pharmacology and experimental verification. [Methods] The potential targets of quercetin were predicted by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and Swiss Target Prediction system. The targets related to BCM were retrieved from Human Gene Database(GeneCards) and Online Mendelian Inheritance in Man(OMIM). Cytoscape 3.7.0 software was used to construct the protein-protein interaction(PPI) network of quercetin and BCM intersection targets. R software and Bioconductor installation package were used to perform gene oncology(GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis， binding molecular docking to explore the binding effect of quercetin and key target proteins in the pathway. Methyl thiazolyl tetrazolium(MTT) assay， wound healing assay， Transwell assay and Western blot were used to explore the mechanism of quercetin inhibiting BCM. [Results] There were 112 intersection targets of quercetin and BCM， KEGG enrichment analysis suggested that focal adhesion(FAs) was the key pathway of quercetin treatment for BCM， and molecular docking results indicated that quercetin strongly binds to the key target of FAs pathway. MTT assay， wound healing assay and Transwell assay showed that quercetin could inhibit the proliferation， migration and invasion ability of BCAP-37 and 4T1 cells(P＜0.05). Western blot showed that quercetin inhibited the activation of sarcoma gene(SRC)， focal adhesion kinase(FAK) and protein kinase B(Akt)， and decreased the expression of phosphatidylinositol-3-kinase(PI3K) protein in FAs pathway(P＜0.05). [Conclusion] Quercetin can inhibit BCM by reducing the activity of SRC/FAK/PI3K signaling pathway. |
|
查看全文
查看/发表评论 下载PDF阅读器 |
| 关闭 |