Lidocaine exerts potential anti-tumor effects on various cancer cell lines, and its intravesical instillation is considered safer than intravenous administration for bladder cancer. However, the mechanisms underlying its anti-tumor effects have not been fully elucidated. Here, we aimed to elucidate the anti-tumor molecular mechanisms of lidocaine in bladder cancer cells and a xenograft model to substantiate the efficacy of its intravesical administration. We investigated the anti-proliferative and autophagyinducing activities of lidocaine in Nara Bladder Tumor No. 2 (NBT-II) rat bladder carcinoma cells using cell viability, flow cytometry, a wound healing assay, and western blotting. We also established a xenograft mouse model of bladder cancer, and cancer growth was examined using in vivo bioluminescence imaging. Lidocaine decreased cell viability, induced G0/G1 phase cell cycle arrest, and inhibited cell migration partially via glycogen synthase kinase (GSK) 3β phosphorylation. Moreover, a combination of lidocaine and SB216763 (a GSK3β inhibitor) suppressed autophagy-related protein expression. Bafilomycin-A1 with lidocaine significantly enhanced microtubule-associated protein 1A/1B-light chain (LC3B) expression; however, it decreased LC3B expression in combination with 3-methyladenine compared to lidocaine alone. In the xenograft mouse model, the bladder cancer volume was reduced by lidocaine. Overall, lidocaine exerts anti-proliferative effects on bladder cancer via an autophagy-inducing mechanism.
利多卡因对多种癌细胞系具有潜在抗肿瘤作用，其膀胱灌注给药方式相较于静脉给药被认为对膀胱癌更为安全。然而，其抗肿瘤作用机制尚未完全阐明。本研究旨在阐明利多卡因在膀胱癌细胞及异种移植模型中的抗肿瘤分子机制，以验证其膀胱灌注给药的有效性。我们通过细胞活力检测、流式细胞术、划痕实验及蛋白质印迹法，探究了利多卡因对Nara膀胱肿瘤2号（NBT-II）大鼠膀胱癌细胞系的抗增殖及自噬诱导活性。同时建立膀胱癌异种移植小鼠模型，并采用活体生物发光成像技术监测肿瘤生长。结果显示，利多卡因通过部分介导糖原合成酶激酶（GSK）3β磷酸化，降低细胞活力、诱导G0/G1期细胞周期阻滞并抑制细胞迁移。此外，利多卡因与GSK3β抑制剂SB216763联用可抑制自噬相关蛋白表达。巴弗洛霉素A1与利多卡因联用能显著增强微管相关蛋白1A/1B-轻链（LC3B）表达；但与3-甲基腺嘌呤联用时，相较于单独使用利多卡因，LC3B表达出现下降。在异种移植小鼠模型中，利多卡因有效抑制了膀胱癌体积增长。综上所述，利多卡因通过诱导自噬机制对膀胱癌发挥抗增殖作用。
肿瘤(癌症)患者之家