Ribeiro Eduarda, Costa Barbara, Marques Lara, Vasques-Nóvoa Francisco, Vale Nuno
PerMed Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Plácido da Costa, 4200-450 Porto, Portugal.
CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal.
J Clin Med. 2024 Jul 14;13(14):4113. doi: 10.3390/jcm13144113.
: 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). : 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. : 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. : 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.
本研究探讨血管扩张剂药物作为辅助治疗手段用于治疗泌尿系统癌症的潜力,特别是与抗肿瘤药物5-氟尿嘧啶(5-FU)联合使用时的潜力。本研究评估了西地那非、替唑生坦和左西孟旦单独使用以及与5-FU联合使用对泌尿系统癌细胞系的细胞毒性作用。评估包括MTT试验、集落形成试验和伤口愈合试验,分别用于确定细胞活力、增殖能力和迁移行为。西地那非和替唑生坦显示出有限的细胞毒性作用,而左西孟旦表现出中等程度的抗癌活性。左西孟旦与5-FU联合使用表现出相加作用,增强了对癌细胞的细胞毒性,同时对正常细胞具有保护作用。左西孟旦还抑制细胞迁移和增殖,可能是通过涉及调节环磷酸腺苷(cAMP)水平和一氧化氮生成的机制实现的。研究结果表明,左西孟旦可与5-FU联合使用,以降低5-FU的所需剂量,从而在不影响治疗效果的情况下将副作用降至最低。本研究为提高泌尿系统癌症患者的治疗效果提供了新的视角。