Inhibitory Effects Of Apatinib On Vasculogenic Mimicry Of Malignant Melanoma Cells And The Mechanism

Objective:To explore the effect of apatinib on the formation of vasculogenic mimicry(VM)in a malignant melanoma cell line and its related mechanisms.Methods: MUM-2B cells cultured in three-dimensional Matrigel were treated with varying concentrations(0,0.01,0.05,0.1,0.5 ?mol/L)of apatinib to test the 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 and CD31-PAS dual staining were performed to assess the expression of VEGFR-2,ERK-1/2,PI3 K,and MMP-2,and formation of VM.Results: 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 apatinibtreated 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,PI3 K,and MMP-2.Conclusion: 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.