Elucidating the Potential Targets and Mechanisms of Bisphenol A-Induced Prostate Cancer Based on Network Toxicology and Molecular Docking AnalysesOA
Background:Bisphenol A(BPA)is a widely used industrial chemical and endocrine-disrupting compound,and accumulating evidence suggests that it may contribute to prostate cancer progression;however,the underlying molecular mechanisms remain incompletely elucidated.This study aimed to elucidate the molecular targets and signaling pathways underlying BPA-induced prostate cancer progression.Methods:In this study,an integrated strategy combining network toxicology,molecular docking,and molecular dynamics simulations was employed to identify potential BPA-related targets and signaling pathways involved in prostate cancer.Candidate targets were retrieved from public databases,followed by protein-protein interaction network analysis to screen key hub genes.Functional assays were performed to evaluate the effects of BPA on prostate cancer cell migration,invasion,epithelial-mesenchymal transition(EMT),and phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT)signaling,and an in vivo mouse model was used to assess the impact of BPA exposure and PI3K inhibition on tumor progression.Results:Eighteen BPA-related core targets were identified,among which androgen receptor(AR),matrix metalloproteinase 9(MMP9),matrix metalloproteinase 2(MMP2),kallikrein-related peptidase 3(KLK3),and hypoxia-inducible factor 1 alpha(HIF1A)emerged as key hub genes.Computational analyses indicated stable predicted interactions between BPA and these proteins.Functionally,BPA exposure promoted prostate cancer cell invasion and EMT,which were associated with activation of the PI3K/AKT and MMP signaling pathways,whereas the PI3K inhibitor LY294002 effectively attenuated BPA-induced invasive phenotypes in vitro and reduced tumor progression in vivo.Conclusions:Collectively,these findings provide mechanistic insights into BPA-driven prostate cancer progression and highlight the value of network toxicology-based approaches in environmental toxicology research.
Ashuai Du;Dianbin Guo;Dongbo Yuan;Kai Li;Yuanyuan Luo;Songsong Tan;Xuchao Dai;Bo Yu;Wanxiang You;Junjie Zhao;Bo Yan;Kehua Jiang;Xiaofei Fan;Jianguo Zhu
Department of Infection,Guizhou Provincial People’s Hospital,Guiyang,ChinaShandong Medical College,No.5460,Second Ring South Road,Jinan,ChinaDepartment of Urology,Guizhou Provincial People’s Hospital,Guiyang,ChinaDepartment of Urology,GuiZhou University Medical College,Guiyang,ChinaDepartment of Urology,GuiZhou University Medical College,Guiyang,ChinaDepartment of Urology,Guizhou Provincial People’s Hospital,Guiyang,ChinaDepartment of Urology,GuiZhou University Medical College,Guiyang,ChinaGraduate School,Zunyi Medical University,Zunyi,ChinaDepartment of Urology,Dejiang County People’s Hospital of Guizhou Province,Dejiang,ChinaYantai Yuhuangding Hospital,Yantai,ChinaDepartment of Urology,Guizhou Provincial People’s Hospital,Guiyang,ChinaDepartment of Urology,Guizhou Provincial People’s Hospital,Guiyang,ChinaShandong Medical College,No.5460,Second Ring South Road,Jinan,ChinaDepartment of Urology,Guizhou Provincial People’s Hospital,Guiyang,China
医药卫生
Bisphenol Aprostate cancernetwork toxicologyphosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT)signalingLY294002
《Oncology Research》 2026 (5)
P.801-824,24
supported by the Guizhou Provincial Basic Research Program(ZK[2025]-505)National Natural Science Foundation of China(82160551)Guizhou Provincial Key Technology R&D Program(ZSYS[2025]-031)Guizhou Provincial Science and Technology Support Plan Program([2025]-132)Medical Research Union Fund for High-quality Health Development of Guizhou Province(2024GZYXKYJJXM0054)Guizhou Provincial People’s Hospital Talent Fund Project([2023]-17)National Natural Science Foundation of China(82303301)Natural Science Foundation of Shandong Province,China(grant no.ZR2022MH261)Yantai Science and Technology Innovation Development Plan,China(Grant No.2022JCYJ040).
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