Tamoxifen was widely applied in the therapy of estrogen receptor (ER)‐positive breast cancer. With the purpose of determining the potential impacts of quercetin on its effectiveness, MCF‐7 cells were selected as the in vitro model and several cellular biological behaviors (ie, cell proliferation, migration, invasion, cycle, apoptosis, and oxidative stress) were investigated. As results, quercetin showed contrasting dose‐response to cellular behaviors dependent on the ROS‐regulated p53 signaling pathways. In detail, quercetin promoted cell proliferation and inhibited cell apoptosis at low concentrations, whereas high‐concentration resulted in apoptosis induction. Moreover, quercetin at a low concentration significantly inhibited tamoxifen‐induced antiproliferation in MCF‐7 cells, whereas high concentrations enhanced cell apoptosis in a synergetic manner. The real‐time quantitative polymerase chain reaction analysis further implied that quercetin exerted its dual roles in tamoxifen‐induced antiproliferative effects by regulated the gene expression involved in cell metastasis, cycle, and apoptosis through the ER pathways. Our present study provides a considerable support to the combination of quercetin and tamoxifen on human ER‐positive breast carcinoma management.

中文翻译：

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槲皮素对他莫昔芬在雌激素受体阳性乳腺癌治疗中的疗效发挥双向调节作用：一项体外研究

他莫昔芬被广泛应用于雌激素受体（ER）阳性乳腺癌的治疗。为了确定槲皮素对其有效性的潜在影响，选择 MCF-7 细胞作为体外模型，并研究了几种细胞生物学行为（即细胞增殖、迁移、侵袭、循环、凋亡和氧化应激） . 结果，槲皮素对依赖于 ROS 调节的 p53 信号通路的细胞行为显示出对比的剂量反应。具体而言，槲皮素在低浓度时促进细胞增殖并抑制细胞凋亡，而高浓度导致细胞凋亡诱导。此外，低浓度的槲皮素可显着抑制他莫昔芬诱导的 MCF-7 细胞增殖，而高浓度以协同方式增强细胞凋亡。实时定量聚合酶链反应分析进一步表明，槲皮素通过内质网通路调节参与细胞转移、周期和凋亡的基因表达，从而在他莫昔芬诱导的抗增殖作用中发挥双重作用。我们目前的研究为槲皮素和他莫昔芬联合治疗人类 ER 阳性乳腺癌提供了相当大的支持。