Enhancing Urological Cancer Treatment: Leveraging Vasodilator Synergistic Potential with 5-FU for Improved Therapeutic Outcomes

Autores da FMUP

• Francisco Aguiar Vasques Novoa Faria

  Autor

• Nuno Filipe De Sousa Vale

  Autor

Participantes de fora da FMUP

• Ribeiro, Eduarda
• Costa, Barbara
• Marques, Lara

Unidades de investigação

• Cirurgia e Fisiologia

• Laboratório Associado RISE- Rede de Investigação em Saúde

  

  Investigador

  Fernando Carlos De Landér Schmitt

• Medicina da Comunidade, Informação e Decisão em Saúde

• RISE-Health

  

  Investigador

  Fernando Carlos De Landér Schmitt

Abstract

Backgroud: This study investigates the potential of vasodilator drugs as additive therapy in the treatment of urological cancers, particularly in combination with the antineoplastic agent 5-fluorouracil (5-FU). Methods: The study evaluated the cytotoxic effects of sildenafil, tezosentan and levosimendan alone and in combination with 5-FU on urological cancer cell lines. The assessment included MTT assays, colony formation assays and wound healing assays to determine cell viability, proliferative capacity, and migratory behavior, respectively. Results: Sildenafil and tezosentan showed limited cytotoxic effects, while levosimendan demonstrated moderate anticancer activity. The combination of levosimendan and 5-FU exhibited an additive interaction, enhancing cytotoxicity against cancer cells while sparing normal cells. Levosimendan also inhibited cell migration and proliferation, potentially through mechanisms involving the modulation of cAMP levels and nitric oxide production. Conclusions: The findings suggest that levosimendan can be used in conjunction with 5-FU to reduce the required dose of 5-FU, thereby minimizing side effects without compromising therapeutic efficacy. This study offers a new perspective for enhancing therapeutic outcomes in patients with urological cancers.

Keywords

• bladder cancer; combination therapy; drug repurposing; in vitro; prostate cancer