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丹参改善乳腺癌患者生存率,二氢丹参酮I诱导乳腺癌细胞铁死亡和凋亡。

Danshen Improves Survival of Patients With Breast Cancer and Dihydroisotanshinone I Induces Ferroptosis and Apoptosis of Breast Cancer Cells.

作者信息

Lin Yu-Shih, Shen Yi-Chia, Wu Ching-Yuan, Tsai Ying-Ying, Yang Yao-Hsu, Lin Yin-Yin, Kuan Feng-Che, Lu Cheng-Nan, Chang Geng-He, Tsai Ming-Shao, Hsu Cheng-Ming, Yeh Reming-Albert, Yang Pei-Rung, Lee I-Yun, Shu Li-Hsin, Cheng Yu-Ching, Liu Hung-Te, Wu Yu-Huei, Wu Yu-Heng, Chang De-Ching

机构信息

Department of Pharmacy, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan.

Institute of Molecular Biology, National Chung Cheng University, Chiayi, Taiwan.

出版信息

Front Pharmacol. 2019 Oct 31;10:1226. doi: 10.3389/fphar.2019.01226. eCollection 2019.

DOI:10.3389/fphar.2019.01226
PMID:31736748
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6836808/
Abstract

Danshen (salvia miltiorrhiza Bunge) is widely used in traditional Chinese medicine. However, it is definite clinical effort and mechanism on breast cancer is unclear. In our study, we used the real-world database to investigate protective effort of danshen in the breast cancer patients through using population-based data from the Taiwan National Health Insurance Research Database (NHIRD). , human breast cancer cells (MCF-7 cells and MDA-MB-231 cells) were used to investigate the effect and the underlying mechanism through XTT assay, flow cytometry, glutathione peroxidase (GPX) activity assay, GSH (reduced glutathione)/GSSG (oxidized glutathione), malondialdehyde (MDA), and western blot analysis. The effect was investigated through a xenograft nude mouse model. We found that dihydroisotanshinone I (DT), a pure compound present in danshen, can inhibit the growth of breast carcinoma cells, including MCF-7 cells and MDA-MB-231 cells. Moreover, DT induced apoptosis and ferroptosis in these breast cancer cells. DT also repressed the protein expression of GPX4 (Glutathione peroxidase 4). For study, DT treatment also significantly inhibited the final tumor volume without adverse effects in a xenograft nude mouse model. In conclusion, danshen has protective efforts in breast cancer patients, which could be attributed to DT through inducing apoptosis and ferroptosis of breast cancer cells.

摘要

丹参(丹参)在传统中医中被广泛应用。然而,其对乳腺癌的确切临床作用及机制尚不清楚。在我们的研究中,我们使用真实世界数据库,通过利用来自台湾国民健康保险研究数据库(NHIRD)的基于人群的数据,调查丹参对乳腺癌患者的保护作用。此外,使用人乳腺癌细胞(MCF-7细胞和MDA-MB-231细胞),通过XTT法、流式细胞术、谷胱甘肽过氧化物酶(GPX)活性测定、GSH(还原型谷胱甘肽)/GSSG(氧化型谷胱甘肽)、丙二醛(MDA)以及蛋白质印迹分析来研究其作用及潜在机制。通过异种移植裸鼠模型研究其效果。我们发现丹参中的一种纯化合物二氢异丹参酮I(DT)可抑制乳腺癌细胞的生长,包括MCF-7细胞和MDA-MB-231细胞。此外,DT诱导这些乳腺癌细胞凋亡和铁死亡。DT还抑制了GPX4(谷胱甘肽过氧化物酶4)的蛋白表达。在异种移植裸鼠模型中,DT治疗也显著抑制了最终肿瘤体积且无不良反应。总之,丹参对乳腺癌患者有保护作用,这可能归因于DT诱导乳腺癌细胞凋亡和铁死亡。

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