Targeting RAGE: A Novel Therapeutic Strategy Against AGE-Mediated Prostate Cancer Progression

Overview

Purpose: The accumulation of advanced glycation end products (AGEs) and their interaction with the receptor for AGEs (RAGE) have been implicated in the progression of prostate cancer (PCa), the second most diagnosed cancer in men worldwide. However, therapeutic strategies targeting RAGE remain underexplored, representing a critical gap in current cancer treatment approaches. This study aimed to investigate the role of the AGE-RAGE signaling pathway in PCa progression, focusing on how RAGE inhibition affects cell migration and how RAGE knockdown influences both migration and proliferation. Methods: RAGE inhibition was achieved using TTP -488 in DU145 cells, and a migration assay as sessed cell migration in response to the following treatments: no treatment (NT), the negative control; AGEs, the positive control; TTP -488; and AGEs & TTP -488. RAGE knockdown was performed via shRNA transfection in LNCaP cells, confirmed by Western Blot a nalysis. A Trypan Blue Proliferation assay evaluated cell growth in LNCaP shRAGE and shControl cells, while a migration assay determined migration in those cells. It was hypothesized that RAGE inhibition and knockdown would reduce PCa cell migration, with knockdown specifically reducing proliferation. Results: ANOVA and post -hoc analyses revealed that disrupting AGE -RAGE signaling via inhibition and genetic knockdown effectively mitigates cell migration, with knockdown also significantly hindering cell prol iferation. These findings support the research hypothesis. Conclusion: Targeting RAGE in PCa reveals a transformative therapeutic approach to control tumor progression and metastasis, set to redefine cancer treatment globally. Future studies should explore combining RAGE disruption with conventional treatments like chemotherapy.