Drug repositioning in metastatic prostate cancer based on protein- protein interaction network: Computational and in vitro analysis.

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.