Abstract
Purpose:
Angiogenesis is a prerequisite for the growth and metastasis of solid tumors. Targeting the proliferation of tumor neovasculature will form an effective anti-cancer therapy. ProAgio is a noval anti-angiogenesis agent that targets Integrins ανβ3 of endothelial cells. In this study, we investigate the effect of the noval anti-angiogenesis agent on human uveal melanoma, mouse melanoma and human/mouse vascular endothelia cells, and screen the sensitivity of tumor cells for the further in vivo experiment.<br />
Methods:
Primary human uveal melanoma cells Mel290, Mel270, OMM3, 02-1486, mouse melanoma Queens, mouse vascular endothelium sVEC and human vascular endothelium HUVEC were subcultured in 6-well-plates and treated with 5μm ProAgio or equal volume of PBS as control for 24 hours after more than 90% confluence. Harvested cells were stained with Caspase 3, CXCR4 and VEGFR2. The stained cells were acquired by FACScanto and analyzed by FlowJo software.<br />
Results:
Comparing with the PBS control, ProAgio resulted in the elevated level of caspase 3 in vascular endothelia HUVEC and sVEC, the unchanged level of caspase 3 in human uveal melanoma and mouse melanoma cells. ProAgio decreased the level of CXCR4 in human uveal melanoma OMM3 and mouse vascular endothelium sVEC, also reduced the level of VEGFR2 in human uveal melanoma OMM3 and 02-1486, and vascular endothelia HUVEC, sVEC.<br />
Conclusions:
ProAgio effectively caused the apoptosis in human and mouse vascular endothelia, not human uveal melanoma in vitro, suppressed the expression of VEGFR2 related with integrins ανβ3 and the migration indicator CXCR4 in vascular endothelia and some types of human uveal melanoma cells. We are able to select human uveal melanoma cells whose expressions of VEGFR2 and CXCR4 can be inhibited by ProAgio for the animal model, in purpose to know the effect of ProAgio on tumor growth and metastasis in vivo.<br />