Elucidating the Potential Targets and Mechanisms of Bisphenol A-Induced Prostate Cancer Based on Network Toxicology
Ashuai Du1, Dianbin Guo2, Dongbo Yuan3
1Department of Infection, Guizhou Provincial People's Hospital, Guiyang, China.
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.
Insights
Bisphenol A (BPA) promotes prostate cancer progression by activating key molecular targets and signaling pathways, including the PI3K/AKT pathway. Inhibiting this pathway reduced tumor growth, offering insights into environmental toxicology.
Area of Science:
- Environmental toxicology
- Molecular biology
- Cancer research
Background:
- Bisphenol A (BPA) is an endocrine-disrupting chemical linked to prostate cancer progression.
- Molecular mechanisms underlying BPA's role in prostate cancer are not fully understood.
Purpose of the Study:
- To identify molecular targets and signaling pathways involved in BPA-induced prostate cancer progression.
- To investigate the mechanistic role of BPA in prostate cancer using integrated computational and experimental approaches.
Main Methods:
- Network toxicology, molecular docking, and molecular dynamics simulations were used to identify BPA-related targets.
- Protein-protein interaction network analysis identified key hub genes.
- Functional assays assessed BPA's effects on prostate cancer cell invasion, migration, epithelial-mesenchymal transition (EMT), and PI3K/AKT signaling.
- An in vivo mouse model evaluated BPA exposure and PI3K inhibition effects on tumor progression.
Main Results:
- Eighteen BPA-related core targets were identified, with AR, MMP9, MMP2, KLK3, and HIF1A as key hub genes.
- BPA exposure promoted prostate cancer cell invasion and EMT, activating PI3K/AKT and MMP signaling pathways.
- The PI3K inhibitor LY294002 attenuated BPA-induced invasion in vitro and reduced tumor progression in vivo.
Conclusions:
- BPA drives prostate cancer progression through specific molecular targets and signaling pathways.
- Network toxicology approaches are valuable for environmental toxicology research.
- Targeting the PI3K/AKT pathway may offer therapeutic strategies for BPA-related prostate cancer.
