VCOM Louisiana Research Day Program

Pharmacology

Alyaa Gad 1,2 , MD, PhD; Dalal Dawud, B. Pharm 1 ; Emily Schierer 1 , OMS-II; Tanya Kumar 1 , OMS-II; Kasia Michalak 1 , MSc; Zakaria Y. Abd Elmageed, PhD 1 Department of Biomedical Sciences 1 , Edward Via College of Osteopathic Medicine, Monroe, Louisiana; School of Basic Pharmaceutical and Toxicological Sciences 2 , College of Pharmacy, University of Louisiana Monroe, Department of Pharmacology 2 ; Faculty of Medicine, Minia University, Minia, Egypt. 48 SYNERGISTIC EFFECT OF ENZALUTAMIDE AND NEXINHIB-20 IN TREATING CASTRATION-RESISTANT PROSTATE CANCER CELLS.

Background and Aim: Prostate cancer (PCa) is the second leading cause of male related cancer death in the Western world. It accounts for 14% of all new cancer cases in the US. Androgen ablation therapy is the standard treatment for patients with primary PCa. However, most of PCa patients developed to more aggressive castration resistant prostate cancer (CRPC) state that has serious implication on the patient’s survival. At this stage, employing enzalutamide (Xtandi © ) remains one of the most effective therapies for CRPC treatment. However, resistance is developed against this therapy. Therefore, the aim of this study was to evaluate the effect of combining a neutrophil exocytosis inhibitor, Nexinhib-20, with enzalutamide in CRPC cells. Methods: Cell proliferation, clonogenic, scratch assays were performed and Western blot analysis was conducted on individual and combined treatment of the two drugs in PC-3 and CWR-22RV1 cells. Results: Our results demonstrate that the individual treatment of Nexinhib-20 and enzalutamide exerted antiproliferative and antimigratory effects. However, a synergistic effect was observed when the two drugs were combined. The combined drugs inhibited the

expression of Rab27a protein and the activity of ERK1/2. Conclusion: These findings suggest that the combination of enzalutamide with Nexinhib-20 could be a potential therapeutic alternative to combat enzalutamide resistance by targeting multiple pathways.

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