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黑升麻对乳腺癌细胞中雌激素受体(ERα)和孕激素受体(PR)调节的影响。

The effects of black cohosh on the regulation of estrogen receptor (ERα) and progesterone receptor (PR) in breast cancer cells.

作者信息

Szmyd Monica, Lloyd Victoria, Hallman Kelly, Aleck Katie, Mladenovik Viktoria, McKee Christina, Morse Mia, Bedgood Tyler, Dinda Sumi

机构信息

Biomedical and Therapeutic Sciences, School of Health Sciences.

Prevention Research Center.

出版信息

Breast Cancer (Dove Med Press). 2018 Jan 18;10:1-11. doi: 10.2147/BCTT.S144865. eCollection 2018.

Abstract

The North American plant , also known as black cohosh (BC), is a herb that recently has gained attention for its hormonal effects. As the usage of hormone replacement therapy is declining due to its adverse effects in women with cancer, many are turning to herbal remedies like BC to treat menopausal symptoms. It is crucial to determine whether the effects of BC involve estrogen receptor-alpha (ERα). Previous studies from our laboratory have shown ERα to be a possible molecular target for BC. In this study, we examined the effects of BC (8% triterpene glycosides) alone and in combination with hormones and antihormones on the cellular viability, expression of ERα and progesterone receptor (PR)-A/B, and cytolocalization of ERα in ER (+) and PR-A/B (+) T-47D breast cancer cells. Cells were cultured and proteins were extracted and quantified. Western blot analysis revealed alterations in the expression of ERα and PR after treatment with BC (5-100 µM). BC induced a concentration-dependent decrease in ERα and PR protein levels when compared to the control. Image cytometric analysis with propidium iodide staining was used to enumerate changes in T-47D cell number and viability. A decrease in T-47D cell viability was observed upon treatment with 5-100 µM BC. The ideal concentration of BC (100 µM) was used in combination with hormones and antihormones in an effort to further understand the possible similarities between this compound and other known effectors of ERα and PR. After a 24-hour concomitant treatment with and/or in combination of BC, estradiol, ICI 182, 780, and Tamoxifen, downregulation of ERα and PR protein levels was observed. Delineating the role of BC in the regulation of ERα, PR, as well as its mechanisms of action, may be important in understanding the influence of BC on hormone receptors in breast cancer.

摘要

这种北美植物,也被称为黑升麻(BC),是一种最近因其激素作用而受到关注的草药。由于激素替代疗法对癌症女性患者有不良影响,其使用量正在下降,许多人转而使用像黑升麻这样的草药疗法来治疗更年期症状。确定黑升麻的作用是否涉及雌激素受体α(ERα)至关重要。我们实验室之前的研究表明ERα可能是黑升麻的分子靶点。在本研究中,我们研究了单独使用黑升麻(8%三萜糖苷)以及与激素和抗激素联合使用对ER(+)和PR-A/B(+) T-47D乳腺癌细胞的细胞活力、ERα和孕激素受体(PR)-A/B的表达以及ERα的细胞定位的影响。培养细胞并提取和定量蛋白质。蛋白质印迹分析显示,用黑升麻(5-100µM)处理后,ERα和PR的表达发生了改变。与对照组相比,黑升麻诱导ERα和PR蛋白水平呈浓度依赖性下降。使用碘化丙啶染色的图像细胞术分析来确定T-47D细胞数量和活力的变化。用5-100µM黑升麻处理后,观察到T-47D细胞活力下降。使用黑升麻的理想浓度(100µM)与激素和抗激素联合使用,以进一步了解该化合物与ERα和PR的其他已知效应器之间可能存在的相似性。在用黑升麻、雌二醇、ICI 182,780和他莫昔芬联合和/或同时处理24小时后,观察到ERα和PR蛋白水平下调。阐明黑升麻在ERα、PR调节中的作用及其作用机制,对于理解黑升麻对乳腺癌激素受体的影响可能很重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c788/5779278/cbadc2423301/bctt-10-001Fig1.jpg

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