| Melanoma is the first most lethal type of skin cancer with a low5-year survival rate.In addition,the incidence of melanoma has contimued to increase in recent years.The surgical therapy has a good clinical effect for patients with early stage melanoma;however,it can result in bad prognosis while tumor metastasis in melamoma.Moreover,there is no effective drug in clinic used for the treatment of metastatic melanoma.Tumor blood vessels can supply for oxygen and nutrients to maintaining tumor growth,and a dissemination route for tumor distance metastasis.Melanoma is a type of vascular dependent tumor,and angiogenesis plays an important role in tumor cell proliferation and metastasis by the supplement of nutrients.Patients with melanoma often develop resistance to the anti-angiogenic drugs that used in clinic.Therefore,there is an urgent need to develop more effective drugs for malignant melanoma treatment.Dipalmitoyl phosphatidic acid(DPPA)is an intermediate metabolite of glycerophosphatidyl.As a second messenger,DPPA plays an important role in many physiological processes.DPPA can regulate drug penetration into the cells through the cell membrane and regulate Bcl-2 expression in a cell type-dependent manner.Our previous reports also indicated that DPPA inhibits tumor growth in breast cancer by suppressing angiogenesis and tumor cell proliferation.However,the regulatory effect of DPPA on melanoma development has not been reported.In this study,we try to explore the effect of DPPA on the growth and metastasis of melanoma and further clarify the underline regulatory mechanisms.In this study,the mouse subcutaneous xenograft tumor model,mouse tail vein lung metastasis mode and melanoma cells were exployed to explore the inhibition effect on tumor growth and metastasis.The chicken embryo blood island formation assay,in vivo matrigel plug angiogenesis assay,rat aortic ring assay,and in vitro cell migration and tube formation of vascular endothelial to explore the inhibition effects of DPPA on angiogenesis.Analysis the results of Angiogenesis-related factors q RT-PCR chip in the HUVECs treated with DPPA and DMSO,and further verified using western blotting to find out the target gene of DPPA in angiogenesis.Then,cell migration and tube formation assays were used to confirm the function of target gene onmangiogenesis in vitro.This study demonstrated that DPPA inhibit tumor growth and metastasis mainly through suppressing angiogenesis by activating CXCL10/CXCR3 signaling,but not inhibit cell viability,migration and invasion of tumor cells in melanoma. |
