硬角提取物通过抑制核因子-κB 信号通路抑制三阴性和 Her-2 乳腺癌细胞的侵袭和上皮间质转化。

Hard antler extract inhibits invasion and epithelial-mesenchymal transition of triple-negative and Her-2 breast cancer cells by attenuating nuclear factor-κB signaling.

机构信息

Department of Breast Surgery, The First Hospital of Jilin University, Changchun, 130021, China.

Institute of Special Animal and Plant Sciences of CAAS, Changchun, 130112, China.

出版信息

J Ethnopharmacol. 2021 Apr 6;269:113705. doi: 10.1016/j.jep.2020.113705. Epub 2020 Dec 18.

DOI:10.1016/j.jep.2020.113705

PMID:33346025

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Hard antler extract (HAE) is a traditional Chinese medicine and has potent antitumor, antioxidative, anti-inflammatory, and immunomodulatory activities. Previous studies have demonstrated that HAE can inhibit human prostate cancer metastasis and murine breast cancer proliferation. However, the effect of HAE on human breast cancer cells has not been clarified.

AIM OF THE STUDY

To investigate the effects and underlying mechanism of HAE on self-renewal of stem-like cells and spontaneous and transforming growth factor (TGF)-β1-enhanced wound healing, invasion and epithelial-mesenchymal transition (EMT) in breast cancer cells.

METHODS

HAE was prepared from sika deer by sequential enzymatic digestions and the active compounds were determined by HPLC. The effects of HAE on the viability, mammosphere formation, wound healing and invasion of MDA-MB-231 and SK-BR3 cells were determined. The impact of HAE treatment on spontaneous and TGF-β1-promoted EMT and the nuclear factor (NF)-κB signaling in breast cancer cells was examined by quantitative RT-PCR and western blotting.

RESULTS

Treatment with HAE at varying concentrations did not change the viability of breast cancer cells. However, HAE at 0.25 or 0.5 mg/mL significantly reduced the number and size of formed mammospheres, and inhibited spontaneous and TGF-β1-enhanced wound healing, invasion and EMT in MDA-MB-231 and SK-BR3 cells in a dose-dependent manner. TGF-β1 treatment significantly decreased IκBα expression and increased NF-kBp65 phosphorylation in breast cancer cells, indicating that TGF-β1 enhanced NF-κB signaling. In contrast, HAE treatment attenuated the spontaneous and TGF-β1-enhanced NF-κB signaling in breast cancer cells.

CONCLUSION

Our data indicated that HAE inhibited the self-renewal of stem-like cells and spontaneous and TGF-β1-enhanced wound healing, invasion and EMT in breast cancer cells by attenuating the NF-κB signaling in vitro.

摘要

民族药理学相关性

鹿角提取物（HAE）是一种传统的中药，具有强大的抗肿瘤、抗氧化、抗炎和免疫调节活性。先前的研究表明，HAE 可以抑制人前列腺癌转移和鼠乳腺癌增殖。然而，HAE 对人乳腺癌细胞的影响尚未阐明。

研究目的

研究 HAE 对乳腺癌细胞自我更新以及自发和转化生长因子（TGF）-β1 增强的伤口愈合、侵袭和上皮-间充质转化（EMT）的影响及其潜在机制。

方法

HAE 由梅花鹿通过连续酶解制备，通过 HPLC 确定其活性化合物。通过测定 HAE 对 MDA-MB-231 和 SK-BR3 细胞活力、乳腺球形成、伤口愈合和侵袭的影响来研究 HAE 的作用。通过定量 RT-PCR 和 Western blot 检测 HAE 处理对乳腺癌细胞自发和 TGF-β1 促进的 EMT 以及核因子（NF）-κB 信号的影响。

结果

用不同浓度的 HAE 处理不会改变乳腺癌细胞的活力。然而，HAE 在 0.25 或 0.5mg/mL 时，显著减少了形成的乳腺球的数量和大小，并以剂量依赖性方式抑制了 MDA-MB-231 和 SK-BR3 细胞的自发和 TGF-β1 增强的伤口愈合、侵袭和 EMT。TGF-β1 处理显著降低了乳腺癌细胞中 IκBα 的表达并增加了 NF-κBp65 的磷酸化，表明 TGF-β1 增强了 NF-κB 信号。相反，HAE 处理减弱了乳腺癌细胞中的自发和 TGF-β1 增强的 NF-κB 信号。