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

• Published in: Cytokine (Philadelphia, Pa.) Vol. 184; p. 156771
• Main Authors: Yao, Ningning, Ma, Qingyue, Yi, Wendan, Liu, Yichong, Zhang, Qian, Gao, Xiaodi, Zhao, Xintong, Wang, Haowen, Lei, Ke, Sui, Aihua, Luo, Wenjuan
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2024
• Subjects: Akt/mTOR; Ang-1; Angiopoietin-1 - metabolism; Animals; Antineoplastic Agents - pharmacology; Artesunate; Artesunate - pharmacology; Artesunate - therapeutic use; Carcinogenesis - drug effects; Carcinogenesis - genetics; Carcinogenesis - metabolism; Carcinogenesis - pathology; Cell Line, Tumor; Cell Movement - drug effects; Cell Proliferation - drug effects; Choroidal melanoma; Epithelial-mesenchymal transition; Epithelial-Mesenchymal Transition - drug effects; Female; Humans; Melanoma - drug therapy; Melanoma - genetics; Melanoma - metabolism; Melanoma - pathology; Mice; Mice, Inbred BALB C; Mice, Nude; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction - drug effects; TOR Serine-Threonine Kinases - metabolism; Xenograft Model Antitumor Assays; Epithelial-mesenchymal transition; Ang-1; Choroidal melanoma; Akt/mTOR; Artesunate
• DOI: 10.1016/j.cyto.2024.156771
• ISSN: 1043-4666; 1096-0023

[Display omitted] 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.