Sánchez-Olivares Paula, Silva-Nolasco Aniela M, de la Cruz-Morcillo Miguel A, García-Martínez María Mercedes, Pinedo-Serrano Alejandro, Carmona Manuel, Galán-Moya Eva M
Cancer Pathophysiology and Therapy Lab, Institute of Biomedicine (IB-UCLM) Universidad de Castilla-La Mancha, Albacete, Spain.
Institute for Regional Development (IDR), Universidad de Castilla-La Mancha, Albacete, Spain.
J Cell Mol Med. 2024 Dec;28(24):e70294. doi: 10.1111/jcmm.70294.
Colorectal cancer is the third most commonly diagnosed cancer worldwide and the second most common cause of cancer-related death in both men and women. Although a number of treatments are available to combat this malignancy, the antimetabolite 5-fluorouracil has been the cornerstone of therapy since its synthesis in the 1950s. Unfortunately, the prolonged use of 5-fluorouracil can lead to chemoresistance, which has prompted research into combination regimens to improve efficacy and quality of life and reduce resistance. Here, we evaluated the synergistic potential of two compounds isolated from guayule, and argentatins A and B, alone and in combination with 5-fluorouracil in a panel of colorectal cancer cell lines. Cell viability assays showed that the combination treatment (argentatin A with 5 fluorouracil) significantly enhanced cytotoxicity, especially in RKO, where the analysis using the Bliss independence model indicated a remarkable synergistic effect with the lowest doses of both compounds. In contrast to the combination with argentatin B, in which the additive effect was only found in the HCT-116 cell line. Finally, immunocytometric analysis revealed that combination treatments induced higher rates of apoptosis than single-agent treatments. Collectively, our findings indicate that argentatins A and B may enhance the anti-tumour effects of 5-fluorouracil and may represent a promising strategy to improve the efficacy of anticancer therapies based on this antimetabolite.
结直肠癌是全球第三大常见诊断癌症，也是男性和女性癌症相关死亡的第二大常见原因。尽管有多种治疗方法可对抗这种恶性肿瘤，但自20世纪50年代合成以来，抗代谢物5-氟尿嘧啶一直是治疗的基石。不幸的是，长期使用5-氟尿嘧啶会导致化疗耐药，这促使人们研究联合治疗方案以提高疗效和生活质量并降低耐药性。在此，我们评估了从银胶菊中分离出的两种化合物——银胶菊素A和B单独以及与5-氟尿嘧啶联合在一组结直肠癌细胞系中的协同潜力。细胞活力测定表明，联合治疗（银胶菊素A与5-氟尿嘧啶）显著增强了细胞毒性，尤其是在RKO细胞系中，使用布利斯独立模型分析表明，两种化合物的最低剂量具有显著的协同作用。与与银胶菊素B联合不同，后者仅在HCT-116细胞系中发现有加和效应。最后，免疫细胞化学分析显示，联合治疗诱导的凋亡率高于单药治疗。总体而言，我们的研究结果表明，银胶菊素A和B可能增强5-氟尿嘧啶的抗肿瘤作用，可能代表一种有前景的策略，以提高基于这种抗代谢物的抗癌疗法的疗效。
