Effect and mechanism of gambogic acid based on heterogeneous transformation of prostate cancer
10.3969/j.issn.1005-4847.2025.09.005
- VernacularTitle:基于前列腺癌异质转化模型探讨藤黄酸作用及机制
- Author:
Minli HUANG
1
;
Mengyao LI
;
Yanzi XING
;
Gen LI
;
Yongbin ZHANG
;
Changhong SHI
Author Information
1. 广州中医药大学动物实验中心,广州 510405;第四军医大学实验动物中心,西安 710032
- Publication Type:Journal Article
- Keywords:
network pharmacology;
gambogic acid;
prostate cancer;
patient-derived tumor organoids;
patient-derived xenograft model
- From:
Acta Laboratorium Animalis Scientia Sinica
2025;33(9):1289-1298
- CountryChina
- Language:Chinese
-
Abstract:
Objective To systematically construct patient-derived tumor organoid(PDO)and patient-derived xenograft(PDX)models of prostate cancer(PCa),and to explore the inhibitory effect and mechanism of gambogic acid(GA)on PCa.Methods The PubChem,SwissTargetPrediction,SuperPred,SEA,GeneCards,OMIM,and STRING databases,and the Venny 2.1.0 online website,Cytoscape 3.8.2,and DAVID software were used to construct a protein-protein interaction network.Gene ontology(GO)and kyoto encyclopedia of genes and genomes(KEGG)enrichment analyses were carried out,and visualization processing was performed to identify the targets and pathways of GA acting on PCa.GA was applied to PDOs and PCa cells(22Rv1,PC3,and DU145)for 48 hours and its effects on cell viability were assessed by CellTiter-Glo and CCK-8 assays.Changes in gene and protein levels of the targets were analyzed by quantitative real-time polymerase chain reaction and Western Blot,respectively.The PDX model was treated with GA and the tumor volume and weight were measured.Changes in expression levels of the targets in tumor tissues were detected by immunohistochemistry.Results Network pharmacology identified signal transducer and activator of transcription 3(STAT3)as the core target of GA inhibiting PCa,related to the hypoxia-inducible factor(HIF)-1α signaling pathway.GA reduced the viability of cells and PDOs and significantly down-regulated HIF-1α,STAT3,and P-STAT3 protein levels.In vivo experiments,tumor volume and weight were significantly reduced in the GA group,and immunohistochemistry showed that STAT3 and HIF-1α expression levels were decreased.Conclusions The clinically representative PDO and PDX models,combined with cell lines,verified the prediction result of network pharmacology,confirming a significant killing effect of GA on PCa,possibly via a mechanism related to the STAT3/HIF-1α signaling pathway.
