Biochanin A Promotes Proliferation that Involves a Feedback Loop of MicroRNA-375 and Estrogen Receptor Alpha in Breast Cancer Cells
Biochanin A Promotes Proliferation that Involves a Feedback Loop of MicroRNA-375 and Estrogen Receptor Alpha in Breast Cancer Cells
复制标题
Biochanin A 促进乳腺癌细胞增殖，涉及 MicroRNA-375 和雌激素受体 Alpha 的反馈环
DOI：
10.1159/000369725
复制
发表时间：
2015-01-01
影响因子：
--
通讯作者：
Huang, Zhaoquan
中科院分区：
文献类型：
--
作者：
Chen, Jian;Ge, Bo;Huang, Zhaoquan
背景：生物粘附素A和芒柄花素是从黄芪根部分离得到的O-甲基化异黄酮类化合物，具有抗肿瘤作用。我们先前的研究发现芒柄花素能激活MCF-7乳腺癌细胞的生长抑制和凋亡活性。我们进行了体内和体外研究，以进一步探讨Bichanin A在促进雌激素受体(ER)阳性细胞增殖方面的潜在作用，并阐明其潜在的机制。方法：用四甲基偶氮唑蓝比色法和流式细胞术检测ER-α阳性乳腺癌细胞(T47D、MCF-7)的增殖和凋亡。用实时定量聚合酶链式反应检测ERα、Bcl2和miR375m RNA水平。与对照组相比，低浓度的Bichanin A(2~6μM)可刺激ERα阳性细胞(T47D、MCF7)增殖。用敏感性较高的T47D细胞研究相关的信号通路。结果：经Bichanin A处理后，ERα、miR375、Bcl2表达明显上调。此外，在体内研究中，用Bichanin A治疗的卵巢切除小鼠的子宫重量显著增加。结论：Bichanin A通过激活miR-375促进ER-α阳性细胞增殖，该机制可能参与了miR-375和ER-α反馈回路。
Background: Biochanin A and formononetin are O-methylated isoflavones that are isolated from the root of Astragalus membranaceus, and have antitumorigenic effects. Our previous studies found that formononetin triggered growth-inhibitory and apoptotic activities in MCF-7 breast cancer cells. We performed in vivo and in vitro studies to further investigate the potential effect of biochanin A in promoting cell proliferation in estrogen receptor (ER)-positive cells, and to elucidate underlying mechanisms. Methods: ERα-positive breast cancer cells (T47D, MCF-7) were treated with biochanin A. The MTT assay and flow cytometry were used to assess cell proliferation and apoptosis. mRNA levels of ERα, Bcl-2, and miR-375 were quantified using real-time polymerase chain reaction. Compared with the control, low biochanin A concentrations (2-6 μM) stimulated ERα-positive cell proliferation (T47D, MCF-7). The more sensitive T47D cells were used to study the relevant signaling pathway. Results: After treatment with biochanin A, ERα, miR-375, and Bcl-2 expression was significantly upregulated. Additionally, in the in vivo studies, uterine weight in ovariectomized mice treated with biochanin A increased significantly. Conclusion: This study demonstrated that biochanin A promoted ERα-positive cell proliferation through miR-375 activation and this mechanism is possibly involving in a miR-375 and ERα feedback loop.