Dihydroartemisinin inhibits melanoma migration and metastasis by affecting angiogenesis.

IF 6.1 2区 医学 Q1 CHEMISTRY, MEDICINAL
Phytotherapy Research Pub Date : 2025-04-01 Epub Date: 2023-11-19 DOI:10.1002/ptr.8065
Zhaoxiang Li, Qi Zhang, Xinyuan Zhang, Quanxin Jin, Qi Yue, Na Li, Huan Liu, Manabu Fujimoto, Guihua Jin
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引用次数: 0

Abstract

Tumor angiogenesis is critical for tumor metastasis by providing oxygen, nutrients, and metastatic pathways. As a potential anti-angiogenic agent, Dihydroartemisinin (DHA) can effectively inhibit tumor metastasis. However, the mechanism how it regulates angiogenesis to affect tumor metastasis has not been fully clarified. To investigate the mechanisms of how DHA regulates melanoma progression. In this study, bioinformatics methods were used to analyze the correlation between angiogenesis and melanoma metastasis. Then, B16F10, A375, HUVECs and mouse metastasis models were adapted to clarify the inhibition of DHA in melanoma. GESA analysis revealed melanoma metastasis significantly positive correlated with angiogenesis. Meanwhile, DHA significantly decreased melanoma nodules and lung wet weight in metastatic tumor mice, and inhibited the expression of the angiogenic marker CD31 in vitro and in vivo. Similarly, DHA inhibited the expression of the angiogenic signal molecule VEGFR2 in A375 and B16F10 cells, and significantly suppressed the formation of their tubular structures. DHA-treated supernatants significantly inhibited the tubule-forming ability as well as lateral and longitudinal migration ability of HUVECs compared with untreated melanoma cell supernatants. Screening yielded the angiogenic pathways HIF-1α/VEGF, PI3K/ATK/mTOR associated with melanoma metastasis, and DHA may inhibit tumor metastasis by inhibiting these angiogenic pathways in melanoma cells to inhibit tumor metastasis. Further non-targeted metabolomics analysis revealed that DHA-treated model mice produced differential metabolites that were also associated with angiogenic pathways. DHA inhibits melanoma invasion and metastasis by mediating angiogenesis. These results have important implications for the potential use of DHA in treatment of melanoma.

双氢青蒿素通过影响血管生成抑制黑色素瘤的迁移和转移。
肿瘤血管生成通过提供氧气、营养和转移途径对肿瘤转移至关重要。双氢青蒿素(DHA)作为一种潜在的抗血管生成药物,能够有效抑制肿瘤的转移。然而,其调控血管生成影响肿瘤转移的机制尚不完全清楚。探讨DHA调控黑色素瘤进展的机制。本研究采用生物信息学方法分析血管生成与黑色素瘤转移的相关性。然后,采用B16F10、A375、HUVECs和小鼠转移模型来阐明DHA在黑色素瘤中的抑制作用。GESA分析显示黑色素瘤转移与血管生成显著正相关。同时,DHA显著降低转移瘤小鼠黑色素瘤结节和肺湿重,抑制血管生成标志物CD31在体内和体外的表达。同样,DHA抑制A375和B16F10细胞中血管生成信号分子VEGFR2的表达,并显著抑制其管状结构的形成。与未处理的黑色素瘤细胞上清液相比,dha处理的上清液显著抑制huvec的小管形成能力以及横向和纵向迁移能力。筛选得到与黑色素瘤转移相关的血管生成通路HIF-1α/VEGF、PI3K/ATK/mTOR, DHA可能通过抑制黑色素瘤细胞中这些血管生成通路来抑制肿瘤转移。进一步的非靶向代谢组学分析显示,dha处理的模型小鼠产生的差异代谢物也与血管生成途径相关。DHA通过介导血管生成抑制黑色素瘤的侵袭和转移。这些结果对DHA在黑色素瘤治疗中的潜在应用具有重要意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Phytotherapy Research
Phytotherapy Research 医学-药学
CiteScore
12.80
自引率
5.60%
发文量
325
审稿时长
2.6 months
期刊介绍: Phytotherapy Research is an internationally recognized pharmacological journal that serves as a trailblazing resource for biochemists, pharmacologists, and toxicologists. We strive to disseminate groundbreaking research on medicinal plants, pushing the boundaries of knowledge and understanding in this field. Our primary focus areas encompass pharmacology, toxicology, and the clinical applications of herbs and natural products in medicine. We actively encourage submissions on the effects of commonly consumed food ingredients and standardized plant extracts. We welcome a range of contributions including original research papers, review articles, and letters. By providing a platform for the latest developments and discoveries in phytotherapy, we aim to support the advancement of scientific knowledge and contribute to the improvement of modern medicine.
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