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.

中文翻译：

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白藜芦醇和阿霉素对膀胱癌细胞的累加作用。

膀胱癌的治疗在临床实践中仍然是一个挑战。可以使用不同的化疗方案；然而，经常观察到肿瘤复发和导致毒性的副作用。阿霉素（DOX）是用于治疗膀胱癌的最有效的抗癌药物之一，可引起慢性心脏毒性，限制了其在临床实践中的使用。白藜芦醇（RES）是一种具有潜在抗膀胱癌活性的天然产物，其代谢快、生物利用度低，需要与化疗药物联合使用以提高其使用效果。我们的研究旨在评估低浓度 DOX (2 µM) 联合 RES（150、200 和 250 µM）对两种膀胱癌细胞系的治疗效果。我们通过进行细胞毒性、克隆形成、氧化应激、细胞迁移、细胞形态和核分裂指数（NDI）测定来研究药物之间的相互作用机制。细胞毒性评估揭示了 RES 和 DOX 对两种细胞系的附加相互作用。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 的组合比 RES 或单独使用 DOX 更有效。总之，低浓度的DOX联合RES可以增强药物对膀胱癌细胞的抗肿瘤作用，从而克服DOX引起的副作用和白藜芦醇的低生物利用度。