VEGF Induce Vasculogenic Mimicry of Choroidal Melanoma through the PI3k Signal Pathway

• Published in: BioMed research international 2019, Vol.2019 (2019), p.1-13
• Main Authors: Jia, Shaoyou, Zhao, Han, Sun, Xiangrong, Gao, Yunxia, Zong, Yao, Xu, Xiaoyan, Luo, Wenjuan
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Angiogenesis; Apoptosis; Biomedical research; Blood; Cancer therapies; Cell Line, Tumor; Cell Proliferation - genetics; Cellular signal transduction; Choroid Neoplasms - genetics; Choroid Neoplasms - pathology; Female; Gelatinase A; Gelatinase B; Gene deletion; Gene expression; Gene Expression Regulation, Neoplastic; Growth factors; Health aspects; Humans; Hypoxia; Immunoglobulins; Kinases; Male; Medical research; Melanoma; Melanoma - genetics; Melanoma - pathology; Metastasis; Migration; Mimicry; mRNA; Neoplasm Proteins - genetics; Neovascularization, Pathologic - genetics; Neovascularization, Pathologic - pathology; Phosphatidylinositol 3-Kinases - genetics; Protein expression; Proteins; Signal transduction; Signal Transduction - genetics; siRNA; Skin cancer; Therapeutic applications; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - genetics; Wound healing
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2019/3909102

Purpose. To explore the effect of VEGF (vascular endothelial growth factor) on the vasculogenic mimicry (VM) formation of Choroidal Melanoma (CM) through PI3k signal pathway, to find novel targets for CM therapy. Methods. This research investigated the molecular mechanism of VEGF promoting VM formation of CM. First, we evaluated the expressions of VEGF in 20 CM specimens by immunohistochemical determination. Then we detected expressions of VEGF, AKT, MT1-MMP, MMP2, and MMP9 of OCM-1 in hypoxia. siRNA was used to inhibit the expression of VEGF, to realize the control of the VM formation. The VM formation was evaluated through wound healing assay, transwell assay, and apoptosis. And then we testify the correlation of the VM and the factors in protein and mRNA level preliminarily. Results. VEGF protein was expressed in CM in all 20 cases of CM, especially along the VM. In hypoxia, the expression of VEGF in OCM-1 increased significantly. VEGF gene deletion reduced the proliferation, migration, and invasion of OCM-1. VEGF gene deletion impaired the expression of invasive associated genes like VEGF, p-AKT, AKT, MT1-MMP, MMP2, and MMP9. These results indicate that VEGF induce VM formation in CM by activating PI3K/AKT signaling pathway. Conclusions. VEGF promoted VM formation by the PI3K signal transduction pathway, indicating a molecular mechanism which may be used to develop new therapeutic targets for the clinical treatment of CM.