In vitro and in vivo apatinib inhibits vasculogenic mimicry in melanoma MUM-2B cells
| Autor: | Jing-Bo Wu, Yu-Juan Zhou, Fang Xie, Zong-Jun-Lin Liu, Rui-Lin Ding, Qing-Lian Wen, Ling-Lin Yang, Shao-Zhi Fu |
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| Rok vydání: | 2018 |
| Předmět: |
Melanomas
0301 basic medicine Skin Neoplasms Pyridines Physiology Angiogenesis Cell Culture Techniques Cancer Treatment lcsh:Medicine Cardiovascular Physiology Mice Phosphatidylinositol 3-Kinases chemistry.chemical_compound 0302 clinical medicine Cell Movement Medicine and Health Sciences Enzyme assays Electron Microscopy Apatinib Colorimetric assays Extracellular Signal-Regulated MAP Kinases lcsh:Science Melanoma Bioassays and physiological analysis Cultured Tumor Cells Staining Mice Inbred BALB C Microscopy MTT assay Multidisciplinary Neovascularization Pathologic Chemistry Phase Contrast Microscopy Cell Staining Oncology Cell Processes 030220 oncology & carcinogenesis Matrix Metalloproteinase 2 Melanoma Cells Female Biological Cultures Signal Transduction Research Article Cell Survival Antineoplastic Agents 03 medical and health sciences Gentamicin protection assay In vivo Cell Line Tumor Animals Humans Neoplasm Invasiveness Vasculogenic mimicry Viability assay Cell Proliferation Matrigel Binding Sites Cell growth lcsh:R Cancers and Neoplasms Biology and Life Sciences Cell Biology Cell Cultures Vascular Endothelial Growth Factor Receptor-2 Research and analysis methods 030104 developmental biology Specimen Preparation and Treatment Biochemical analysis Cancer research lcsh:Q Drug Screening Assays Antitumor Neoplasm Transplantation Developmental Biology |
| Zdroj: | PLoS ONE, Vol 13, Iss 7, p e0200845 (2018) PLoS ONE |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0200845 |
| Popis: | The effect of apatinib on the formation of vasculogenic mimicry (VM) was studied in a malignant melanoma cell line. MUM-2B cells cultured in three-dimensional Matrigel were treated with varying concentrations (0, 0.01, 0.05, 0.1, 0.5 μmol/L) of apatinib to test its effect on VM in vitro, followed by MTT proliferation and transwell invasion assays to determine the effect of apatinib on cell proliferation and invasion of MUM-2B cells. In vivo, we used a melanoma cancer model to test the effect of short-term apatinib (100, 200, 300 mg/kg) treatment on VM. Western blotting, immunohistochemistry staining, and CD31-PAS dual staining were performed to assess the expression of VEGFR-2, ERK-1/2, PI3K, and MMP-2, and formation of VM. The results showed apatinib-treated groups formed a lesser number of VM in 3D matrigel, while the cell viability in MTT proliferation assay and the number of migration cells in transwell invasion assay were significantly lower in apatinib-treated groups. In addition, short-term apatinib treatment inhibited angiogenesis, VM formation, and tumor growth in models of melanoma cancer. Mice in apatinib-treated groups showed a markedly reduced expression of VEGFR-2, ERK-1/2, PI3K, and MMP-2. In summary, apatinib could inhibit the expression of VEGFR-2, and downregulate the ERK1/2/PI3K/MMP-2 signaling cascade, which may be one of the underlying mechanisms by which apatinib inhibits angiogenesis and the development of VM in models of melanoma cancer, and restrains the formation of VM by MUM-2B cells. Apatinib shows inhibitory effects on cell proliferation and invasion of MUM-2B cells, which is a close relationship with the VM. |
| Databáze: | OpenAIRE |
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