网络药理学联合蛋白质组学揭示3-乙酰-11-酮-β-乳香酸通过调节IL-17信号通路抑制前列腺癌进展

Network Pharmacology Combined with Proteomics Reveals That 3‑Acetyl-11-keto-β-boswellic Acid Inhibits the Progression of Prostate Cancer by Regulating the IL-17 Signaling Pathway.

作者信息

Zou Bo, Liu Qizhi, Long Yan, Dai Xinjun, Tian Xuefei, Zhou Qing

机构信息

The First Hospital of Hunan University of Chinese Medicine, Changsha 410007, Hunan, China.

Hunan University of Chinese Medicine, Changsha 410208, Hunan, China.

出版信息

ACS Omega. 2025 May 22;10(21):21813-21822. doi: 10.1021/acsomega.5c01683. eCollection 2025 Jun 3.

DOI:10.1021/acsomega.5c01683

PMID:40488086

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12138829/

Abstract

BACKGROUND

3-acetyl-11-keto-beta-boswellic acid (AKBA) is a monomer extracted from the traditional Chinese herbs of Boswellia that has antitumor effects. However, the therapeutic effects and mechanisms of AKBA in prostate cancer (PCa) are unclear.

OBJECTIVE

To predict the target of AKBA treatment of PCa using network pharmacology methods and validate the predicted targets through CCK-8, flow cytometry, cell scratch test, Transwell chamber assay, and proteomics.

METHODS

The protein-protein interaction (PPI) network was established. Further analysis was performed by gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes for biological functionality and pathway enrichment. CCK-8 assay, flow cytometry, wound healing assay, and Transwell chamber assay were used to detect cell proliferation, apoptosis, invasion, and metastasis, respectively. Transcriptomics was used to detect the effects of AKBA on protein levels in PCa cells.

RESULTS

120 potential targets for the AKBA treatment of PCa were obtained. GO enrichment analysis revealed that the biological processes of AKBA treatment of PCa include the steroid metabolic process, drug response, and fatty acid metabolic process. The results of KEGG enrichment revealed that the IL-17 signaling pathway is the key pathway for the AKBA treatment of PCa. In addition, experimental results demonstrate that AKBA inhibits the proliferation of PCa cells, induces cell apoptosis, and suppresses cell invasion and metastasis. Proteomics identified 119 differentially expressed proteins, which were primarily enriched in pathways closely related to the phogosome, pathways in cancer, IL-17 signaling pathway, spliceosome, PPAR signaling pathway, and HIF-1 signaling pathway.

CONCLUSION

Through the methodologies of network pharmacology and transcriptomics, AKBA may exert its therapeutic effects on PCa by modulating the expression of the IL-17 signaling pathway.

摘要

背景

3-乙酰-11-酮基-β-乳香酸（AKBA）是从乳香这种传统中药中提取的一种具有抗肿瘤作用的单体。然而，AKBA在前列腺癌（PCa）中的治疗效果及机制尚不清楚。

目的

采用网络药理学方法预测AKBA治疗PCa的靶点，并通过CCK-8、流式细胞术、细胞划痕试验、Transwell小室实验和蛋白质组学对预测靶点进行验证。

方法

建立蛋白质-蛋白质相互作用（PPI）网络。通过基因本体论（GO）和京都基因与基因组百科全书进行进一步分析，以实现生物学功能和通路富集。分别采用CCK-8实验、流式细胞术、伤口愈合实验和Transwell小室实验检测细胞增殖、凋亡、侵袭和转移情况。利用转录组学检测AKBA对PCa细胞蛋白质水平的影响。

结果

获得了120个AKBA治疗PCa的潜在靶点。GO富集分析显示，AKBA治疗PCa的生物学过程包括类固醇代谢过程、药物反应和脂肪酸代谢过程。KEGG富集结果显示，IL-17信号通路是AKBA治疗PCa的关键通路。此外，实验结果表明，AKBA可抑制PCa细胞增殖，诱导细胞凋亡，并抑制细胞侵袭和转移。蛋白质组学鉴定出119种差异表达蛋白，这些蛋白主要富集在与吞噬体、癌症通路、IL-17信号通路、剪接体、PPAR信号通路和HIF-1信号通路密切相关的通路中。