■黄芩素,黄芩中发现的最丰富的黄酮类化合物之一,表现出对各种癌症的药理活性。然而,黄芩素治疗去势抵抗性前列腺癌(CRPC)的确切药理机制仍然难以捉摸。本研究旨在通过网络药理学和实验相结合的方法阐明黄芩素抗CRPC的潜在机制。从而为CRPC治疗的研究提供了新的途径。
■使用TCMSP数据库获得黄芩素的药理学和分子性质。黄芩素相关靶标从多个来源收集,包括SwissTargetPrediction,PharmMapper和CTD。与CRPC相关的目标是从DisGeNet获得的,GeneCards,CTD。使用STRING11.5分析蛋白质-蛋白质相互作用(PPI),并利用Cytoscape3.7.2软件探索黄芩素在CRPC上的核心靶标。使用DAVID数据库进行GO和KEGG途径富集分析。进行细胞实验以确认靶标的有效性。
■获得了总共131个用于治疗CRPC的黄芩素的潜在靶标。其中,TP53,AKT1,ALB,CASS3、HSP90AA1等.,被Cytoscape3.7.2认定为核心目标。GO功能富集分析产生926个条目,包括703个生物过程(BP)术语,84个细胞组分(CC)项和139个分子功能(MF)项。KEGG通路富集分析揭示了159条信号通路,主要参与癌症的通路,前列腺癌,AGE-RAGE信号通路在糖尿病并发症中的作用,TP53信号通路,和PI3K-Akt信号通路,等。细胞实验证实黄芩素可抑制CRPC细胞的增殖并诱导细胞周期阻滞在G1期。这种作用可能与TP53/CDK2/细胞周期蛋白E1途径有关。此外,CETSA的结果表明黄芩素可能直接与TP53结合。
■基于网络药理学分析和细胞实验,我们预测并验证了黄芩素治疗CRPC的潜在靶点和相关途径。这种综合方法为阐明黄芩素在CRPC治疗中作用的分子机制提供了科学依据。此外,这些发现为新型抗CRPC药物的研发提供了有价值的见解和参考。
UNASSIGNED: Baicalein, one of the most abundant flavonoids found in Chinese herb Scutellaria baicalensis Georgi, exhibits pharmacological activities against various cancers. However, the precise pharmacological mechanism of baicalein in treating castration-resistant prostate cancer (CRPC) remains elusive. This study aimed to elucidate the potential mechanism of baicalein against CRPC through a combination of network pharmacology and experimental approaches, thereby providing new avenues for research in CRPC treatment.
UNASSIGNED: The pharmacological and molecular properties of baicalein were obtained using the TCMSP database. Baicalein-related targets were collected from multiple sources including SwissTargetPrediction, PharmMapper and CTD. Targets related to CRPC were acquired from DisGeNET, GeneCards, and CTD. The protein-protein interaction (PPI) was analyzed using STRING 11.5, and Cytoscape 3.7.2 software was utilized to explore the core targets of baicalein on CRPC. GO and KEGG pathway enrichment analysis were performed using DAVID database. Cell experiments were carried out to confirm the validity of the targets.
UNASSIGNED: A total of 131 potential targets of baicalein for the treatment of CRPC were obtained. Among them, TP53, AKT1, ALB, CASP3, and HSP90AA1, etc., were recognized as core targets by Cytoscape 3.7.2. GO function enrichment analysis yielded 926 entries, including 703 biological process (BP) terms, 84 cellular component (CC) terms and 139 molecular function (MF) terms. The KEGG pathway enrichment analysis unveiled 159 signaling pathways, mainly involved in Pathways in cancer, prostate cancer, AGE-RAGE signaling pathway in diabetic complications, TP53 signaling pathway, and PI3K-Akt signaling pathway, etc. Cell experiments confirmed that baicalein may inhibit the proliferation of CRPC cells and induce cell cycle arrest in the G1 phase. This effect could be associated with the TP53/CDK2/cyclin E1 pathway. In addition, the results of CETSA suggest that baicalein may directly bind to TP53.
UNASSIGNED: Based on network pharmacology analysis and cell experiments, we have predicted and validated the potential targets and related pathways of baicalein for CRPC treatment. This comprehensive approach provides a scientific basis for elucidating the molecular mechanism underlying the action of baicalein in CRPC treatment. Furthermore, these findings offer valuable insights and serve as a reference for the research and development of novel anti-CRPC drugs.