THE COMBINATION OF DAPT AND ENZALUTAMIDE IMPROVES IN VIVO PC3 PROSTATE TUMORS

CHIMENTO, AGUSTINA; HERRERA, SOFÍA; VITALE, DAIANA L; TESSONE, LICINA; ALANIZ, LAURA D.; CRISTINA, CAROLINA

Congreso; Reunión Anual de Sociedades de Biociencias; 2023

Prostate cancer (PCa) is one of the most frequent cancers among males. New AR inhibitor agents such as Enzalutamide (Enz) have been released; but, their efficacy is insufficient. There is strong evidence that involves Notch pathway in prostate development but its role in PCa generation and progression is poorly understood.We previously demonstrated AR and Notch receptor expression in prostate cancer PC3 cells in vitro and we observed significantly reduced viability of PC3 cells treated both with Enz (p=0.0018;n=3), an inhibitor of Notch signaling DAPT (p=0.0027;n=3) and also with the combined Enz-DAPT treatment (p=0.0043;n=3). In this work, we aimed to study the effect of Notch system inhibition together with Enz treatment in prostate tumor development in vivo. We injected PC3 cells subcutaneously in Nude mice and we treated them three times/week during 3 weeks with DAPT (i.p. 12 mg/kg,n=4), Enz (i.p. 10 mg/kg,n=3) or the combination of Enz-DAPT (n=3). Control animals received vehicle (DMSO) (n=4). No differences were observed in the single treatments, but tumor growth reached a reduction along the second week in the Enz-DAPT animals compared to controls (p