Background: Breast cancer remains a leading cause of cancer-related deaths among women, primarily attributed to the formidable challenge of multidrug resistance, often driven by the overexpression of the ABCB1 gene. background: Breast cancer remains a leading cause of cancer-related deaths among women, primarily attributed to the formidable challenge of multidrug resistance, often driven by the overexpression of the ABCB1 gene. Objective: This study aimed to assess the synergistic effects of siRNA, doxorubicin, and vinorelbine on ABCB1 gene expression and cell viability in doxorubicin-resistant MCF-7/ADR breast cancer cells, with siRNA targeting ABCB1 to reduce its expression and doxorubicin/ vinorelbine to eradicate cancer cells. objective: This study aimed to assess the synergistic effects of siRNA, doxorubicin, and vinorelbine on ABCB1 gene expression and cell viability in doxorubicin-resistant MCF-7/ADR breast cancer cells, with siRNA targeting ABCB1 to reduce its expression and doxorubicin/vinorelbine to eradicate cancer cells. Methods: Our methodology involved culturing MCF-7 and MCF-7/ADR cells in standard cell culture conditions. The synthesized siRNA sequences transfected cells with siRNA at final concentrations of 10, 20, and 30 nM and assessed cell viability using the MTT assay was performed. Real-time PCR was employed to quantify ABCB1 mRNA expression levels. Results: Results indicated that MCF-7/ADR cells exhibited substantial resistance to vinorelbine and doxorubicin compared to MCF-7 cells, displaying resistance at 12.50 μM and 25.00 μM for vinorelbine and 6.25 μM and 25.00 μM for doxorubicin. Remarkably, siRNA treatment effectively reversed drug resistance in MCF-7/ADR cells across all concentrations of vinorelbine and doxorubicin tested. When combined, siRNA, doxorubicin, and vinorelbine yielded a significantly greater reduction in cell viability compared to individual drug treatments, particularly at a 20 μM siRNA concentration. This combination therapy also significantly suppressed ABCB1 gene expression by a factor of 41.48 in MCF-7 cells relative to MCF-7/ADR cells. Conclusion: these findings suggest that combining siRNA, doxorubicin, and vinorelbine holds promise as a therapeutic strategy to overcome ABCB1-mediated multidrug resistance in breast cancer. Further investigations and clinical trials are warranted to evaluate its clinical efficacy rigorously.

中文翻译：

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SiRNA 介导的 ABCB1 敲低增强了多柔比星和长春瑞滨在乳腺癌细胞中的功效

背景：乳腺癌仍然是女性癌症相关死亡的主要原因，这主要归因于多药耐药性的巨大挑战，而这种挑战通常是由 ABCB1 基因的过度表达引起的。背景：乳腺癌仍然是女性癌症相关死亡的主要原因，这主要归因于多重耐药性的巨大挑战，而这种挑战通常是由 ABCB1 基因的过度表达引起的。目的：本研究旨在评估 siRNA、多柔比星和长春瑞滨对多柔比星耐药 MCF-7/ADR 乳腺癌细胞 ABCB1 基因表达和细胞活力的协同作用，其中 siRNA 靶向 ABCB1 降低其表达，多柔比星/长春瑞滨降低其表达。消灭癌细胞。目的：本研究旨在评估 siRNA、多柔比星和长春瑞滨对多柔比星耐药 MCF-7/ADR 乳腺癌细胞中 ABCB1 基因表达和细胞活力的协同作用，其中 siRNA 靶向 ABCB1 降低其表达，多柔比星/长春瑞滨降低其表达。消灭癌细胞。方法：我们的方法涉及在标准细胞培养条件下培养 MCF-7 和 MCF-7/ADR 细胞。合成的 siRNA 序列用终浓度为 10、20 和 30 nM 的 siRNA 转染细胞，并使用 MTT 测定评估细胞活力。采用实时 PCR 来量化 ABCB1 mRNA 表达水平。结果：结果表明，与 MCF-7 细胞相比，MCF-7/ADR 细胞对长春瑞滨和阿霉素表现出显着的耐药性，对长春瑞滨显示出 12.50 μM 和 25.00 μM 的耐药性，对多柔比星在 6.25 μM 和 25.00 μM 的情况下显示出耐药性。值得注意的是，在测试的所有浓度的长春瑞滨和阿霉素中，siRNA 治疗均有效逆转了 MCF-7/ADR 细胞的耐药性。与单独的药物治疗相比，siRNA、阿霉素和长春瑞滨联合使用时，细胞活力显着降低，特别是在 20 μM siRNA 浓度下。相对于 MCF-7/ADR 细胞，这种联合疗法还在 MCF-7 细胞中显着抑制 ABCB1 基因表达 41.48 倍。结论：这些发现表明，结合 siRNA、阿霉素和长春瑞滨有望成为克服 ABCB1 介导的乳腺癌多药耐药性的治疗策略。需要进一步的研究和临床试验来严格评估其临床疗效。