Department of Medical Biology and Genetics, Faculty of Medicine, Gazi University, Ankara, Turkey.
Department of Histology and Embryology, Faculty of Medicine, Gazi University, Ankara, Turkey.
Technol Cancer Res Treat. 2024 Jan-Dec;23:15330338241241245. doi: 10.1177/15330338241241245.
One of the most significant characteristics of cancer is epithelial-mesenchymal transition and research on the relationship between phenolic compounds and anticancer medications and epithelial-mesenchymal transition is widespread. In order to investigate the potential effects of Taxifolin on enhancing the effectiveness of Epirubicin in treating breast cancer, specifically in 4T1 cells and an allograft BALB/c model, the effects of Taxifolin and Epirubicin, both individually and in combination, were examined. Cell viability assays and cytotoxicity assays in 4T1 cells were performed. In addition, 4T1 cells were implanted into female BALB/c mice to conduct studies and evaluate the therapeutic efficacy of Taxifolin and Epirubicin alone or in combination. Tumor volumes and histological analysis were also assessed in mice. To further understand the mechanisms involved, we examined the messenger RNA and protein levels of epithelial-mesenchymal transition-related genes, as well as active Caspase-3/7 levels, using quantitative real-time polymerase chain reaction, western blot, and enzyme-linked immunosorbent assays, respectively. results demonstrated that the coadministration of Taxifolin and Epirubicin reduced cell viability and cytotoxicity in 4T1 cell lines. , coadministration of Taxifolin and Epirubicin suppressed tumor growth in BALB/c mice with 4T1 breast cancer cells. Additionally, this combination treatment significantly increased the levels of active caspase-3/7 and downregulated the messenger RNA and protein levels of N-cadherin, β-catenin, vimentin, snail, and slug, but upregulated the E-cadherin gene. It significantly decreased the messenger RNA levels of the Zeb1 and Zeb2 genes. The and results of our study indicate that the concurrent use of Epirubicin with Taxifolin has supportive effects on breast cancer treatment.
癌症的一个最重要的特征是上皮-间充质转化，并且广泛研究了酚类化合物与抗癌药物和上皮-间充质转化之间的关系。为了研究Taxifolin 增强表阿霉素治疗乳腺癌（特别是在 4T1 细胞和同种异体 BALB/c 模型中的）的效果，我们研究了 Taxifolin 和 Epirubicin 单独和联合的作用。在 4T1 细胞中进行了细胞活力测定和细胞毒性测定。此外，将 4T1 细胞植入雌性 BALB/c 小鼠中进行研究，并评估 Taxifolin 和 Epirubicin 单独或联合使用的治疗效果。还评估了小鼠的肿瘤体积和组织学分析。为了进一步了解所涉及的机制，我们分别使用定量实时聚合酶链反应、western blot 和酶联免疫吸附测定，检查了上皮-间充质转化相关基因的信使 RNA 和蛋白水平以及活性 Caspase-3/7 水平。结果表明，Taxifolin 和 Epirubicin 的联合使用降低了 4T1 细胞系中的细胞活力和细胞毒性。此外，Taxifolin 和 Epirubicin 的联合治疗显著抑制了 BALB/c 小鼠中的肿瘤生长，这些小鼠携带了 4T1 乳腺癌细胞。此外，这种联合治疗显著增加了活性 Caspase-3/7 的水平，并下调了 N-cadherin、β-catenin、vimentin、snail 和 slug 的信使 RNA 和蛋白水平，但上调了 E-cadherin 基因。它显著降低了 Zeb1 和 Zeb2 基因的信使 RNA 水平。我们的研究结果表明，Epirubicin 与 Taxifolin 联合使用对乳腺癌治疗具有支持作用。
