Efficacy and Safety of Resveratrol in the Treatment of Bladder Cancer Derived Organoids

Abstract

Intravesical instillation is a prevalent approach in bladder cancer (BC) management, yet it often causes adverse reactions and drug resistance. Safer and more effective alternative are therefore in urgent need, and resveratrol (RES) emerges as a promising candidate. However, the effectiveness of RES against BC remains unexplored. In this study, BC‐derived organoids (BCOs) were established to evaluate the efficacy of RES in comparison to conventional anti‐BC drugs (epirubicin, cisplatin, gemcitabine, and vinorelbine). After a 96‐hour treatment, RES demonstrated superior anti‐BCOs efficacy (64.00%; 16/25) compared to the other chemotherapeutics (15.38% to 53.85%). 18 BCOs were treated with RES, epirubicin (EPI), or a combination of RES and EPI (RES/EPI) in short‐term (3 h/day for 4 times) to mimic intravesical instillation. RES exhibited the stronger efficacy (44.44%; 8/18) than EPI against BCOs, and the RES/EPI enhanced sensitivity of a single drug (50.00%; 9/18). RES inhibited the activation of β‐catenin/CD44 axis in RES‐sensitive BCOs. The organoid‐forming potential of mouse bladder was preserved after intravesical instillation of RES, and 200 μM RES demonstrated no adverse effects on patient‐derived bladder urothelial organoids. Our findings highlight the potential of RES, particularly in combination with EPI, to improve intravesical instillation outcomes in BC management.This article is protected by copyright. All rights reserved