Ang-1 promotes tumorigenesis and mediates the anti-cancer effects of Artesunate on Choroidal melanoma via the regulation of Akt/mTOR signaling pathway

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine Pub Date : 2024-09-27 DOI:10.1016/j.cyto.2024.156771

Ningning Yao , Qingyue Ma , Wendan Yi , Yichong Liu , Qian Zhang , Xiaodi Gao , Xintong Zhao , Haowen Wang , Ke Lei , Aihua Sui , Wenjuan Luo

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Abstract

The impact of Ang-1 on tumors remains a subject of contention, with its mechanism of action exhibiting complexity in the progression of diverse tumor types. Ang-1 has been shown to promote the progression of glioma, glioma, esophageal and human cervical cancer, whereas it exerts inhibitory effects on the growth of breast and colon cancer. However, the specific function of Ang-1 in CM has not been clarified. This research aims to explore the function of Ang-1 on CM and the underlying mechanism. WB and qPCR were utilized to measure the expression levels of different factors in CM cells. Clonogenic, CCK-8 and Transwell migration assay were used to probe CM cells’ proliferation and migration ability. Xenograft tumor model was used to testify the effect of Ang-1 and Artesunate (ART) on the growth of CM in vivo. We found Ang-1 promoted CM proliferation and migration, while it was inhibited by ART in vitro. Moreover, both ART treatment and Ang-1 knockdown had the effect of suppressing tumor growth in CM xenograft model. Mechanically, Ang-1 activated Akt/mTOR pathway and induced epithelial-mesenchymal transition (EMT) in CM cells. Furthermore, ART regulated Akt/mTOR pathway by decreasing the expression of Ang-1 in CM cells. Ang-1 promotes tumorigenesis of CM by regulating Akt/mTOR pathway, which can be inhibited by ART.

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Ang-1 通过调控 Akt/mTOR 信号通路促进肿瘤发生并介导青蒿琥酯对脉络膜黑色素瘤的抗癌作用

Ang-1 对肿瘤的影响仍是一个争论不休的话题，其作用机制在不同类型肿瘤的发展过程中表现出复杂性。研究表明，Ang-1 能促进胶质瘤、神经胶质瘤、食管癌和人类宫颈癌的进展，而对乳腺癌和结肠癌的生长则有抑制作用。然而，Ang-1 在中医中的具体功能尚未明确。本研究旨在探索 Ang-1 对肿瘤的功能及其内在机制。本研究采用 WB 和 qPCR 方法测定不同因子在 CM 细胞中的表达水平。采用克隆、CCK-8和Transwell迁移试验检测CM细胞的增殖和迁移能力。利用异种移植肿瘤模型检验 Ang-1 和青蒿琥酯（ART）对体内 CM 生长的影响。我们发现 Ang-1 促进了 CM 的增殖和迁移，而 ART 则抑制了 CM 的增殖和迁移。此外，在 CM 异种移植模型中，ART 治疗和 Ang-1 基因敲除均有抑制肿瘤生长的作用。从机制上讲，Ang-1激活了Akt/mTOR通路，诱导了CM细胞的上皮-间质转化（EMT）。此外，ART通过降低Ang-1在CM细胞中的表达来调节Akt/mTOR通路。Ang-1通过调节Akt/mTOR通路促进CM的肿瘤发生，而Akt/mTOR通路可被ART抑制。

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来源期刊

Cytokine 医学-免疫学

CiteScore

7.60

自引率

2.60%

发文量

262

审稿时长

48 days

期刊介绍： The journal Cytokine has an open access mirror journal Cytokine: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. * Devoted exclusively to the study of the molecular biology, genetics, biochemistry, immunology, genome-wide association studies, pathobiology, diagnostic and clinical applications of all known interleukins, hematopoietic factors, growth factors, cytotoxins, interferons, new cytokines, and chemokines, Cytokine provides comprehensive coverage of cytokines and their mechanisms of actions, 12 times a year by publishing original high quality refereed scientific papers from prominent investigators in both the academic and industrial sectors. We will publish 3 major types of manuscripts: 1) Original manuscripts describing research results. 2) Basic and clinical reviews describing cytokine actions and regulation. 3) Short commentaries/perspectives on recently published aspects of cytokines, pathogenesis and clinical results.