Inhibition of PREX1 Reverses Enzalutamide Resistance in Castration-Resistant Prostate Cancer

Purpose

Castration-resistant prostate cancer (CRPC) often progresses despite initial responses to enzalutamide owing to the development of resistance. Our study explored the mechanisms underlying resistance in enzalutamide-resistant prostate cancer cell lines, along with the role of phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchanger 1 (PREX1) in CRPC resistance. Materials and Methods: The sequencing of total RNA was performed to analyze the microarray gene expression profiles. In our colony formation assay, 1,000 cells per well were seeded into six-well plates to evaluate clonogenic survival. Phosphoprotein profiling was conducted to assess specific signaling pathways and estimate cell proliferation rates. Protein expression was analyzed by western blotting, and Rac GTPase activity was measured to evaluate the cellular responses to enzalutamide. Cell invasion was examined using Transwell migration assays. An in vivo model involving the subcutaneous implantation of tumor cells into mice was used to study tumorigenic potential under resistant conditions.