Selective estrogen receptor modulators (SERMs) are steroid analogs with dual functionality, acting as partial estrogen receptor agonists to preserve postmenopausal bone density and as estrogen receptor antagonists in breast tissue. Bazedoxifene acetate (BZA) is an FDA-approved, third-generation SERM used in the treatment of osteoporosis in women. It demonstrates potential as a therapeutic option for breast cancer patients undergoing endocrine therapy. Our study aimed to assess BZA’s effects on Estrogen Receptor Alpha (ERα) and tumor suppressor gene BRCA1 in T-47D and MCF-7 breast cancer cells, using Western blots, cellular viability, apoptosis assays, and RT-qPCR. Cells were cultured in 5% charcoal-stripped fetal bovine serum for six days to deplete endogenous steroids. Following a 24 h exposure to 2 µM BZA (optimal concentration determined from 1 nM–2 µM studies), Western blot analyses revealed reduced ERα and BRCA1 protein levels in both cell lines. ERα decreased by 48–63% and BRCA1 by 61–64%, indicating sensitivity to antiestrogens. Cytolocalization of ERα and BRCA1 remained unchanged after BZA and 17-β-estradiol (E2) treatment. ESR1 mRNA expression correlated with Western blot findings. Image cytometric analysis using the stain, propidium iodide, detected decreased cellular proliferation in T-47D and MCF-7 cells following a 6-day treatment ranging from 1 nM to 2 µM BZA. BZA treatment alone led to a tenfold reduction in cellular proliferation compared to estrogen-treated cells, suggesting antiproliferative effects. Understanding BZA’s modulation of BRCA1 and ERα, along with their mechanistic interactions, is vital for comprehending its impact on breast cancer tumor suppressors and hormone receptors.
选择性雌激素受体调节剂（SERMs）是具有双重功能的类固醇类似物，在绝经后骨密度维持中作为雌激素受体部分激动剂发挥作用，而在乳腺组织中则表现为雌激素受体拮抗剂。醋酸巴多昔芬（BZA）是美国食品药品监督管理局批准的第三代SERM，用于治疗女性骨质疏松症。该药物在乳腺癌患者内分泌治疗中展现出潜在治疗价值。本研究通过蛋白质印迹、细胞活力检测、细胞凋亡实验及实时定量聚合酶链反应，旨在评估BZA对T-47D和MCF-7乳腺癌细胞中雌激素受体α（ERα）及抑癌基因BRCA1的影响。细胞在5%活性炭剥离胎牛血清中培养六天以耗尽内源性类固醇。经2 µM BZA（通过1 nM–2 µM浓度梯度实验确定的最适浓度）处理24小时后，蛋白质印迹分析显示两种细胞系中ERα和BRCA1蛋白水平均下降：ERα降低48–63%，BRCA1降低61–64%，表明细胞对抗雌激素药物具有敏感性。经BZA和17-β-雌二醇（E2）处理后，ERα与BRCA1的细胞定位未发生改变。ESR1 mRNA表达水平与蛋白质印迹结果一致。使用碘化丙啶染料的图像细胞计量分析显示，经1 nM至2 µM浓度范围的BZA处理6天后，T-47D和MCF-7细胞增殖能力下降。单独BZA处理组与雌激素处理组相比，细胞增殖减少十倍，表明其具有抗增殖效应。理解BZA对BRCA1和ERα的调控作用及其机制性相互作用，对于阐明该药物对乳腺癌抑癌基因与激素受体的影响至关重要。
肿瘤(癌症)患者之家