Pharmaceutical Department, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
Pharmaceutical Department, Qingdao Mental Health Center, Qingdao, China.
Braz J Med Biol Res. 2024 Sep 6;57:e13537. doi: 10.1590/1414-431X2024e13537. eCollection 2024.
The clinical application of 5-fluorouracil (5-Fu), a potent chemotherapeutic agent, is often hindered by its well-documented cardiotoxic effects. Nevertheless, natural polyphenolic compounds like resveratrol (RES), known for their dual anti-tumor and cardioprotective properties, are potential adjunct therapeutic agents. In this investigation, we examined the combined utilization of RES and 5-Fu for the inhibition of gastric cancer using both in vitro and in vivo models, as well as their combined impact on cardiac cytotoxicity. Our study revealed that the co-administration of RES and 5-Fu effectively suppressed MFC cell viability, migration, and invasion, while also reducing tumor weight and volume. Mechanistically, the combined treatment prompted p53-mediated apoptosis and autophagy, leading to a considerable anti-tumor effect. Notably, RES mitigated the heightened oxidative stress induced by 5-Fu in cardiomyocytes, suppressed p53 and Bax expression, and elevated Bcl-2 levels. This favorable influence enhanced primary cardiomyocyte viability, decreased apoptosis and autophagy, and mitigated 5-Fu-induced cardiotoxicity. In summary, our findings suggested that RES holds promise as an adjunct therapy to enhance the efficacy of gastric cancer treatment in combination with 5-Fu, while simultaneously mitigating cardiotoxicity.
5-氟尿嘧啶（5-Fu）是一种有效的化疗药物，但其心脏毒性作用已被充分证实，临床应用常受到限制。然而，白藜芦醇（RES）等天然多酚化合物具有双重抗肿瘤和心脏保护作用，是有潜力的辅助治疗药物。在本研究中，我们使用体外和体内模型，研究了 RES 和 5-Fu 联合抑制胃癌的作用，以及它们对心脏细胞毒性的联合影响。研究结果表明，RES 和 5-Fu 的联合应用可有效抑制 MFC 细胞活力、迁移和侵袭，同时降低肿瘤重量和体积。在机制上，联合治疗可通过 p53 介导的细胞凋亡和自噬发挥作用，从而产生显著的抗肿瘤效果。值得注意的是，RES 可减轻 5-Fu 诱导的心肌细胞氧化应激，抑制 p53 和 Bax 的表达，同时上调 Bcl-2 水平。这种有利影响可提高原代心肌细胞活力，减少细胞凋亡和自噬，并减轻 5-Fu 诱导的心脏毒性。综上所述，RES 有望作为辅助治疗药物与 5-Fu 联合使用，增强胃癌治疗的疗效，同时减轻心脏毒性。
