Escola de Farmácia, Departamento de Análises Clínicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais.
Programa de Pós-graduação em Ciências Farmacêuticas (CIPHARMA), Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais.
Anticancer Drugs. 2022 Jan 1;33(1):e389-e397. doi: 10.1097/CAD.0000000000001218.
The treatment of bladder cancer remains a challenge in clinical practice. Different chemotherapeutic protocols can be used; however, it is common to observe tumor recurrence and secondary effects that result in toxicity. Doxorubicin (DOX), one of the most effective anticancer agents used to treat bladder cancer, can cause chronic cardiotoxicity, limiting its use in clinical practice. Resveratrol (RES), a natural product with potential antitumor activity against bladder cancer, is associated with rapid metabolism and low bioavailability and needs to be combined with chemotherapeutic drugs to improve its use. Our study aimed to assess the therapeutic effect of a low concentration of DOX (2 µM) in combination with RES (150, 200 and 250 µM) on two bladder cancer cell lines. We investigated the mechanism of interaction between the drugs by performing cytotoxicity, clonogenic, oxidative stress, cell migration, cell morphology and nuclear division index (NDI) assays. Cytotoxicity evaluation revealed an additive interaction between RES and DOX for both cell lines. Additionally, the results of cell colony formation, oxidative stress, cell migration, cell morphology and NDI assays showed that a combination of DOX and RES was more effective than RES or DOX alone. In conclusion, a low concentration of DOX combined with RES could potentiate the antitumor effects of the drugs on bladder cancer cells, thus overcoming the secondary effects caused by DOX and the low bioavailability of resveratrol.
膀胱癌的治疗仍然是临床实践中的一个挑战。可以使用不同的化疗方案；然而，观察到肿瘤复发和导致毒性的继发性效应是很常见的。阿霉素（DOX）是治疗膀胱癌最有效的抗癌药物之一，但会导致慢性心脏毒性，限制了其在临床实践中的应用。白藜芦醇（RES）是一种具有潜在抗肿瘤活性的天然产物，对膀胱癌具有活性，但由于其代谢迅速和生物利用度低，需要与化疗药物联合使用以提高其应用效果。我们的研究旨在评估低浓度 DOX（2 μM）与 RES（150、200 和 250 μM）联合治疗两种膀胱癌细胞系的治疗效果。我们通过进行细胞毒性、集落形成、氧化应激、细胞迁移、细胞形态和核分裂指数（NDI）测定来研究药物相互作用的机制。细胞毒性评估显示 RES 和 DOX 对两种细胞系均具有相加作用。此外，细胞集落形成、氧化应激、细胞迁移、细胞形态和 NDI 测定的结果表明，DOX 和 RES 的联合使用比 RES 或 DOX 单独使用更有效。总之，低浓度 DOX 与 RES 联合使用可以增强药物对膀胱癌细胞的抗肿瘤作用，从而克服 DOX 引起的继发性效应和白藜芦醇的低生物利用度。
