Extract from Astragalus membranaceus inhibit breast cancer cells proliferation via PI3K/AKT/mTOR signaling pathway.

Extract from Astragalus membranaceus inhibit breast cancer cells proliferation via PI3K/AKT/mTOR signaling pathway.
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黄芪提取物通过PI3K/AKT/mTOR信号通路抑制乳腺癌细胞增殖

DOI:
10.1186/s12906-018-2148-2
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发表时间:
2018-03-09
影响因子:
--
通讯作者:
Xu L
Xu L
中科院分区:
医学3区
文献类型:
--
作者:
Zhou R;Chen H;Chen J;Chen X;Wen Y;Xu L

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研究背景:黄芪(Astragalus membranaceus,AM)是一种常用的中药,作为治疗多种疾病的必备补品已有2000多年的历史。本研究旨在探讨黄芪提取物对乳腺癌细胞的生物学作用及其机制。采用高效液相色谱法对提取物中的主要黄酮类化合物进行分析。采用MTT比色法和形态学观察法检测AM提取物的抗增殖活性。流式细胞仪检测细胞凋亡。结果:HPLC分析表明,AM提取物中含有风铃草素、芒柄花素、毛蕊异黄酮和芒柄花素4种黄酮类化合物。MTT法和形态学观察表明,黄芪提取物对MCF-7、SK-BR-3和MDA-MB-231细胞增殖有抑制作用,且呈剂量依赖性。流式细胞仪分析显示,25 μg/ml和50 μg/ml黄芪提取物处理后,乳腺癌细胞凋亡率明显高于DMSO和空白对照组(均P < 0.05)。结论:黄芪提取物通过PI 3 K/AKT/mTOR信号通路抑制细胞增殖,诱导细胞凋亡,证实了黄芪具有抗肿瘤作用。因此,我们的研究结果提供了一个新的见解抗癌作用的AM提取物作为一个有前途的代理在乳腺癌治疗。
Background:Astragalus membranaceus (AM) is a commonly used herb in traditional Chinese medicine (TCM), which has been used as an essential tonic to treat various diseases for more than 2000 years. In this study, we aimed to investigate the biological effects of extract from AM on breast cancer cell and its mechanism.Methods:To prepare the extract, dried AM were ground and extracted with water extraction-ethanol supernatant method. Then the main isoflavones in the extract was detect by HPLC analysis. Furthermore, the anti-proliferative activity of AM extract was examined by MTT assay and morphological observation. Cell apoptosis was evaluated with flow cytometric analysis. The expressions of total and phosphorylated PI3K, GS3Kβ, Akt and mTOR were determined by western blot analysis.Results:HPLC analysis demonstrated that AM extract contained with four kinds of isoflavones, campanulin, ononin, calycosin and formononetin. The MTT test and morphological observation indicated that cells proliferation of MCF-7, SK-BR-3 and MDA-MB-231were inhibited by AM extract in a dose dependent manner. Furthermore, flow cytometric analysis displayed that after treated with 25 μg/ml and 50 μg/ml AM extract, apoptosis of breast cancer cells was significantly increased as compared with DMSO and blank control group (all p < 0.05). Western blot analysis found that the level of p-PI3K, p-GS3Kβ, p-Akt, and p-mTOR were significantly decreased, but the level of total-mTOR was observably increased as compared with DMSO control group.Conclusions:Taken together, the inhibited cell proliferation and induced cell apoptosis effect of AM extract via PI3K/AKT/mTOR pathway confirmed the anti-tumor potential of AM. Therefore, our findings provide a new insight into anti-cancer effect of AM extract as a promising agent in breast cancer treatment.
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