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Updated: May 31, 2026
Pre-clinical Orthotopic Murine Model of Human Prostate Cancer
Published on: August 29, 2016
Drug repositioning in metastatic prostate cancer based on protein- protein interaction network: Computational and in
Zakie Saadat1, Seyed Mahdi Ahmadi1, Mohammad Javad Bazyari1
1Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Abstract:
Metastasis is a big challenge for prostate cancer patients that reduces their overall survival from 98.2% to 30%. Therefore, it is important to find the underlying mechanism driving metastasis and find a drug that can prevent cell invasion, migration, and metastasis. Here, we analyzed publicly available expression data of primary and metastasized tissue of Prostate cancer extracted from the GEO database. The obtained Differentially Expressed Genes (DEGs) were used to construct the Protein-Protein Interaction (PPI) and functional networks. These DEGs were enriched in pathways such as blood vessel development, and mesenchyme migration which are involved in the process of Prostate cancer metastasis. The hub genes in the constructed PPI network were subjected to the DrugBank query to find candidate drugs with potential inhibitory effects on metastasis. We found that Artesunate can target three hub genes: CSRP1, FLNA, and TPM1. Finally, we validate this finding by in vitro assessments on the LNCaP cell line. We observed that 2.5 mg/ml Artesunate in the scratch assay reduced the scratch closure rate by about 50% compared to the control in 48 h. These findings suggest that Artesunate may be a promising therapeutic agent for inhibiting prostate cancer metastasis.
Insights
Metastasis significantly impacts prostate cancer survival. This study identified Artesunate as a potential drug targeting key genes involved in prostate cancer cell invasion and migration, showing promise for inhibiting metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Prostate cancer metastasis drastically reduces patient survival.
- Understanding metastasis mechanisms is crucial for developing effective treatments.
Purpose of the Study:
- To identify key genes and pathways driving prostate cancer metastasis.
- To discover potential drugs that can inhibit prostate cancer cell invasion and migration.
Main Methods:
- Analysis of gene expression data from primary and metastatic prostate cancer tissues.
- Construction of Protein-Protein Interaction (PPI) and functional networks using Differentially Expressed Genes (DEGs).
- In silico drug screening using DrugBank and in vitro validation using scratch assays.
Main Results:
- DEGs were enriched in pathways like blood vessel development and mesenchyme migration.
- Hub genes CSRP1, FLNA, and TPM1 were identified as potential targets.
- Artesunate demonstrated a significant reduction in prostate cancer cell migration in vitro.
Conclusions:
- Artesunate shows potential as a therapeutic agent to inhibit prostate cancer metastasis.
- Targeting hub genes like CSRP1, FLNA, and TPM1 may be a viable strategy.
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