Treatment Of Orthotopic Implantation Of Human Glioma Cells In Nude Mice With Nordy And Its Effects On Expression Of FPR And Angiogenesis

Malignant glioma,the one of the most common brain tumors,is characterized by its rapid growth,high invasiveness to normal brain tissues and active neovascularization. Therefore,it is of great importance to explore novel targets for therapeutics for malignant glioma.The glioma model in nude mice is reliable animal model for the study of the tumorigenesis and biological characteristics and therapy.Owing to the special microenvironment of the human brain,it is very important to establish a glioma orthotopic transplantation model in animal for therapeutic study and new drug development.Formylpeptide receptor(FPR) is a G-protein-coupled receptor(GPCR) that mediates chemotaxis of phagocytic leukocytes induced by bacterial peptide N-formyl-methionyl-leucyl-phenylalanine(fMLF).FPR is expressed by highly malignant gliomas cells but not by less aggressive glioma cells or by normal human astrocytes and was related to the degree of malignancy.The result confirmed a novel function of FPR that promotes tumor growth and active neovascularization in glioma,and therefore,FPR might be a novel immunopharmocological target for cancer therapy.Nordihydroguaiaretic acid(NDGA) is a natural lipoxygenase(LO) inhibitor.Our previous studies have shown that NDGA possessed a marked differentiation inducing effect and the growth inhibitory effect on human glioma cells.Based on the structure of natural NDGA,we synthesized its chiral compound Nordy.Our prvious studies in multiple models showed its potential anti-tumor effects.For a better understanding of FPR functions in malignant glioma and the mechanism of Nordy anti-cancer effects which might be related to angiogenesis mediated by FPR,in the present study we investigated the two of effects:firstly,to observe the relationship between FPR expression and production and of vascular endothelial growth factor(VEGF) in human glioma cells line U87 orthotopic transplantation tumors in nude mouse brain,and to explore the potential roles of FPR during angiogenesis of malignant glioma.Then,to observe the effects of a synthetic compound Nordy on the expression of formylpeptide receptor(FPR) in orthotopic transplantation tumors of human glioma cells in nude mice brain and to explore the possible mechamism of Nordy anti-caner effect.The main results and conclusions are as follows:1,U87 cells and its orthotopic transplantation tumor had the formyl-peptide receptor (FPR),whose expression and activation was closely correlated with production of VEGF. Thus it might be of much importance in progression and angiogenesis of malignant gliomas.2,Nordy had potential therapeutic effects on orthotopic implanted glioma in nude mouse brain.The inhibitory effects of Nordy on FPR expression and production of VEGF might be one of the mechamisms for its anti-cancer effects.