双氢青蒿素通过调节血管内皮生长因子和 MMP-2/-9 抑制乳腺癌血管生成

IF 2.1 4区 医学 Q3 PHARMACOLOGY & PHARMACY Fundamental & Clinical Pharmacology Pub Date : 2023-07-25 DOI:10.1111/fcp.12941
Qi Rao, He Yu, Ruochan Li, Bin He, Yuxue Wang, Xiaohong Guo, Gang Zhao, Fenghua Wu
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引用次数: 0

摘要

背景:双氢青蒿素(DHA)是一种青蒿素衍生物,因其抗疟特性而闻名。它还具有抗肿瘤和抗血管生成的潜力。然而,它在抑制乳腺癌血管生成方面的具体作用尚不十分清楚:我们旨在研究 DHA 对乳腺癌的抗血管生成作用,并探索其作为治疗药物的潜力。我们的目标是评估 DHA 对 MDA-MB-231 细胞诱导的新生血管生成的影响,评估其对血管内皮细胞的血管萌发和管形成的影响,并分析关键血管生成相关蛋白的表达:方法:我们使用鸡绒毛膜(CAM)模型培养 MDA-MB-231 细胞并用 DHA 处理。我们评估了血管新生情况,并用 DHA 处理过的细胞培养基培养血管内皮细胞,以评估血管萌芽和管形成情况。用 Western 印迹法分析了血管内皮生长因子、MMP-2 和 MMP-9 的蛋白表达水平:结果:DHA能明显减轻MDA-MB-231细胞诱导的新生血管形成。它还抑制了暴露于经 DHA 处理的细胞介质中的 HUVEC 细胞的血管萌发和管形成。此外,DHA 还能降低血管内皮生长因子、MMP-2 和 MMP-9 蛋白的表达。从机理上讲,DHA抑制了肿瘤细胞中PI3K、AKT、ERK和NF-κB蛋白的磷酸化:我们的研究提供了 DHA 对乳腺癌血管生成有抑制作用的证据。这些发现支持了 DHA 作为抗乳腺癌药物的潜力,值得进一步研究其治疗应用。
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Dihydroartemisinin inhibits angiogenesis in breast cancer via regulating VEGF and MMP-2/-9

Background

Dihydroartemisinin (DHA) is an artemisinin derivative known for its antimalarial properties. It has also shown potential as an anti-tumor and anti-angiogenic agent. However, its specific role in inhibiting angiogenesis in breast cancer is not well understood.

Objectives

We aimed to investigate the anti-angiogenesis effect of DHA on breast cancer and explore its potential as a therapeutic drug. Our objectives were to assess the impact of DHA on neovascularization induced by MDA-MB-231 cells, evaluate its effects on vessel sprout and tube-formation in vascular endothelial cells, and analyze the expression of key angiogenesis-related proteins.

Methods

Using a chicken chorioallantoic membrane (CAM) model, we cultured MDA-MB-231 cells and treated them with DHA. We assessed neovascularization and cultured vascular endothelial cells with DHA-treated cell media to evaluate vessel sprout and tube-formation. Protein expression levels of VEGF, MMP-2, and MMP-9 were analyzed using Western blotting.

Results

DHA significantly attenuated neovascularization induced by MDA-MB-231 cells. It also suppressed vessel sprout and tube-formation of HUVEC cells when exposed to DHA-treated cell media. Furthermore, DHA downregulated the expression of VEGF, MMP-2, and MMP-9 proteins. Mechanistically, DHA inhibited the phosphorylation of PI3K, AKT, ERK, and NF-κB proteins in tumor cells.

Conclusions

Our study provides evidence of the inhibitory effect of DHA on breast cancer angiogenesis. These findings support the potential of DHA as an anti-breast cancer drug and warrant further investigation for its therapeutic applications.

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来源期刊
CiteScore
5.30
自引率
6.90%
发文量
111
审稿时长
6-12 weeks
期刊介绍: Fundamental & Clinical Pharmacology publishes reports describing important and novel developments in fundamental as well as clinical research relevant to drug therapy. Original articles, short communications and reviews are published on all aspects of experimental and clinical pharmacology including: Antimicrobial, Antiviral Agents Autonomic Pharmacology Cardiovascular Pharmacology Cellular Pharmacology Clinical Trials Endocrinopharmacology Gene Therapy Inflammation, Immunopharmacology Lipids, Atherosclerosis Liver and G-I Tract Pharmacology Metabolism, Pharmacokinetics Neuropharmacology Neuropsychopharmacology Oncopharmacology Pediatric Pharmacology Development Pharmacoeconomics Pharmacoepidemiology Pharmacogenetics, Pharmacogenomics Pharmacovigilance Pulmonary Pharmacology Receptors, Signal Transduction Renal Pharmacology Thrombosis and Hemostasis Toxicopharmacology Clinical research, including clinical studies and clinical trials, may cover disciplines such as pharmacokinetics, pharmacodynamics, pharmacovigilance, pharmacoepidemiology, pharmacogenomics and pharmacoeconomics. Basic research articles from fields such as physiology and molecular biology which contribute to an understanding of drug therapy are also welcomed.
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