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评估具有雌激素活性的中草药在乳腺癌中的安全性。

Evaluation of the safety profiles of estrogenic Chinese herbal medicines in breast cancer.

机构信息

Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; State Key Laboratory of Phytochemistry and Plant Resources in West China (CUHK), The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.

Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.

出版信息

Phytomedicine. 2019 Mar 15;56:103-117. doi: 10.1016/j.phymed.2018.10.003. Epub 2018 Oct 8.

Abstract

BACKGROUND

An increasing number of breast cancer patients in Asian countries has been found to consume dietary supplements including phytoestrogen-rich Chinese herbal medicines with an expectation to alleviate the side effects of conventional cancer therapies.

PURPOSE

The question of whether estrogenic Chinese herbal medicines are beneficial or detrimental to the health of breast cancer patients remains uncertain.

STUDY DESIGN

The present study aimed at establishing a systematic approach to look at the safety profiles of estrogenic Chinese herbal medicines (CHM).

METHODS

The effects of estrogenic CHM on the growth of human breast cancer cells as well as the progression of breast tumors in mice have been investigated.

RESULTS

Our results demonstrated that among 10 selected estrogenic CHM, the aqueous extracts of Cistanche deserticola (CD) and Dioscorea opposita (DO) at 0.4 to 1.6 mg/ml significantly stimulated cell viability in both estrogen receptor (ER)-positive (MDA-MB-361 and MCF-7) and ER-negative (SKBR3 and MDA-MB-231) breast cancer cells. However, results from animal studies showed that no significant difference was found on the size of mouse 4T1 breast tumors in CD- and DO-treated mice when compared with the control group, while the number of proliferative cells were found to be increased in DO-treated group. Besides, CD and DO treatments induced significant immunomodulatory effects on 4T1 tumor-bearing mice by increasing the production of cytokines IL-2 and IFN-γ and modulation of regulatory T-cells. Furthermore, CD and DO treatments did not stimulate, but in fact suppressed human triple-negative MDA-MB-231 breast xenografts growth in immunodeficiency mice.

CONCLUSION

The considerable concerns on the use of CD and DO in breast cancer patients could be relieved to some extents upon the findings of this pre-clinical study. The potential harmful effects of estrogenic Chinese herbal medicines on breast cancer growth should be verified in both cell-based and tumor-bearing mice models.

摘要

背景

在亚洲国家,越来越多的乳腺癌患者服用包括富含植物雌激素的中草药在内的膳食补充剂,以期缓解常规癌症治疗的副作用。

目的

关于雌激素类中草药对乳腺癌患者的健康是有益还是有害,目前仍不确定。

研究设计

本研究旨在建立一种系统的方法来评估雌激素类中草药(CHM)的安全性。

方法

研究了雌激素类 CHM 对人乳腺癌细胞生长以及小鼠乳腺癌肿瘤进展的影响。

结果

我们的研究结果表明,在 10 种选定的雌激素类 CHM 中,0.4-1.6mg/ml 的肉苁蓉(CD)和山药(DO)水提物显著刺激了雌激素受体(ER)阳性(MDA-MB-361 和 MCF-7)和 ER 阴性(SKBR3 和 MDA-MB-231)乳腺癌细胞的活力。然而,动物研究结果表明,与对照组相比,CD 和 DO 处理组的小鼠 4T1 乳腺癌肿瘤大小没有显著差异,而 DO 处理组的增殖细胞数量增加。此外,CD 和 DO 处理通过增加细胞因子 IL-2 和 IFN-γ的产生以及调节调节性 T 细胞,对 4T1 荷瘤小鼠产生显著的免疫调节作用。此外,CD 和 DO 处理并没有刺激,实际上抑制了免疫缺陷小鼠中人类三阴性 MDA-MB-231 乳腺癌异种移植物的生长。

结论

在这项临床前研究的基础上,一定程度上减轻了人们对 CD 和 DO 在乳腺癌患者中应用的担忧。应在基于细胞和荷瘤小鼠模型中验证雌激素类中草药对乳腺癌生长的潜在有害作用。

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