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基于网络药理学和生物信息学的甘松饮对肾透明细胞癌的作用机制及实验验证

The mechanism of action and experimental verification of Gan-song Yin on renal clear cell carcinoma based on network pharmacology and bioinformatics.

作者信息

Jiang Wenjie, Yuan Ling, Liu Qian, Li Xiangyang, Yang Yifan, Li Jiaqing, Jiao Taiqiang, Niu Yang, Zhang Lei, Dou Hongli, Nan Yi

机构信息

Key Laboratory of Ningxia Minority Medicine Modernization Ministry of Education, Ningxia Medical University, Yinchuan, 750004, Ningxia, China.

School of Traditional Chinese Medicine, Ningxia Medical University, Yinchuan, 750004, Ningxia, China.

出版信息

Discov Oncol. 2024 Feb 28;15(1):52. doi: 10.1007/s12672-024-00909-1.

Abstract

BACKGROUND

Gan-song Yin (GSY) is originated from the scripture "Gan-song Pills", a medical work of the Ningxia ethnic minorities, and its treatment of kidney diseases has good results. Its method of treating Renal clear cell carcinoma (KIRC) is still unknown, nevertheless.

METHODS

Firstly, utilizing a network pharmacology strategy to screen GSY for active components and targets and looking up KIRC-related targets in GeneCards and GEO databases. Secondly, protein interaction networks were constructed and analyzed for GO and KEGG enrichment. Molecular docking was then performed and clinical and other correlations of the network pharmacology results were analyzed using bioinformatic analysis methods. Finally, we performed in vitro cellular experiments with 786-O cells and ACHN cells to validate the results of network pharmacology and bioinformatic analysis.

RESULTS

With the help of network pharmacological analysis, six hub targets were eliminated. Bioinformatics study revealed that the hub targets has clinically significant clinical guiding importance. The results showed that GSY inhibited the proliferation of 786-O cells and ACHN cells, induced cell apoptosis, blocked cell cycle, and reduced cell colony formation ability. qRT-PCR results showed that GSY promoted the expression of ALB and CASP3 genes, and inhibited the expression of EGFR, JUN, MYC and VEGFA genes. Western blot results showed that GSY could promote the expression of ALB and CASP3 protein, and inhibit the expression of EGFR, JUN, MYC and VEGFA protein.

CONCLUSIONS

Network pharmacology and bioinformatics analysis showed that GSY could act on multiple targets through a variety of components to achieve the effect of treating KIRC. In this study, we confirmed that GSY inhibits KIRC by regulating the expression of core targets through in vitro cellular experiments, thus providing a reference for subsequent related studies.

摘要

背景

甘松饮(GSY)源自宁夏少数民族医学著作《甘松丸》,其对肾脏疾病的治疗效果良好。然而,其治疗肾透明细胞癌(KIRC)的方法尚不清楚。

方法

首先,利用网络药理学策略筛选GSY的活性成分和靶点,并在GeneCards和GEO数据库中查找KIRC相关靶点。其次,构建蛋白质相互作用网络并进行GO和KEGG富集分析。然后进行分子对接,并使用生物信息学分析方法分析网络药理学结果的临床及其他相关性。最后,我们用786-O细胞和ACHN细胞进行体外细胞实验,以验证网络药理学和生物信息学分析的结果。

结果

借助网络药理学分析,排除了六个枢纽靶点。生物信息学研究表明,这些枢纽靶点具有重要的临床指导意义。结果显示,GSY抑制786-O细胞和ACHN细胞的增殖,诱导细胞凋亡,阻断细胞周期,并降低细胞集落形成能力。qRT-PCR结果显示,GSY促进ALB和CASP3基因的表达,并抑制EGFR、JUN、MYC和VEGFA基因的表达。蛋白质印迹结果显示,GSY可促进ALB和CASP3蛋白的表达,并抑制EGFR、JUN、MYC和VEGFA蛋白的表达。

结论

网络药理学和生物信息学分析表明,GSY可通过多种成分作用于多个靶点,从而达到治疗KIRC的效果。在本研究中,我们通过体外细胞实验证实GSY通过调节核心靶点的表达来抑制KIRC,从而为后续相关研究提供参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d90/10902223/6f27ced8765c/12672_2024_909_Fig1_HTML.jpg

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