title: Inhibition of tumor growth and vasculogenic mimicry by curcumin through down-regulation of the EphA2/PI3K/MMP pathway in a murine choroidal melanoma model.
abstract: 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. Sixty mice were given subretinal injection with B16F10 cells and divided into a treatment and a control group. Curcumin was 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 was administered to the control group. Immunohistochemical and histochemical double staining were ued 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 were analyzed using immunohistochemical staining; mRNA levels were measured using real-time PCR analysis. 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). In conclusion, curcumin has the ability to inhibit the growth of engrafted melanoma VM channels through the regulation of vasculogenic factors that could be 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.
authors.affiliation: Eye Center of Tianjin Medical University, Tianjin, China.
authors.forename: Lu-Xia
authors.initials: LX
authors.lastname: Chen
authors.forename: Yan-Jin
authors.initials: YJ
authors.lastname: He
authors.forename: Shao-Zhen
authors.initials: SZ
authors.lastname: Zhao
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Wu
authors.forename: Jian-Tao
authors.initials: JT
authors.lastname: Wang
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Zhu
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Lin
authors.forename: Bao-Cun
authors.initials: BC
authors.lastname: Sun
authors.forename: Xiao-Rong
authors.initials: XR
authors.lastname: Li
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002830:Choroid Neoplasms / Q000098:blood supply* / Q000473:pathology; D003474:Curcumin / Q000494:pharmacology*; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008546:Melanoma, Experimental / Q000098:blood supply* / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic; D010503:Periodic Acid-Schiff Reaction / Q000379:methods; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D036104:Receptor, EphA2 / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D058539:Phosphatidylinositol 3-Kinase; D036104:Receptor, EphA2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D003474:Curcumin