Inhibition of tumor growth and vasculogenic mimicry by cucumin through down-regulation of the EphA2/PI3K/MMP pathway in choroidal melanoma model

Purpose This study aims to investigate the underlying mechanism by which curcumin inhibits tumor growth and reduces vasculogenic mimicry (VM) in a murine choroidal melanoma model.
Methods Sixty mice were given subretinal injection with B16F10 cells and divided into a treatment and a control group. Curcumin is administered to the treatment group once a day at a dose of 100 mg/kg for 18 days starting at d3 (the day of inoculation is designated as d0); an equivalent volume of poloxamer-F68 is administered to the control group. Double immunostaining is performed to detect the different blood supply patterns. The amounts of epithelial cell kinase (EphA2), phosphatidylinositol-3-kinase (PI3K), and matrixmetalloproteinase-2 and -9 (MMP-2, MMP-9) proteins expressed in the tumor tissue are analyzed using immunohistochemical staining; mRNA levels are measured using real-time PCR analysis.
Results Results indicate that the tumor volume is reduced (P=0.000) and that the numbers of VM (P=0.000), mosaic vessels (P=0.031), and endothelium-dependent vessels (P=0.000) are significantly decreased by curcumin (P=0.001). The expression levels of EphA2, PI3K, MMP-2, and -9 are also lower in the treatment group than in the control group (P=0.001); similarly, mRNA levels in the treatment group are lower than those in the control group (P=0.000).
Conclusion In conclusion, curcumin inhibits the growth of engrafted melanoma and VM channels through the regulation of vasculogenic factors, an activity related to the down-regulation of the EphA2/PI3K/MMPs signaling pathway. Thus, curcumin has the potential of being a clinical inhibitor of VM of choroidal melanoma.