Purine Analogue 6-Methylmercaptopurine Riboside Inhibits Early and Late Phases of the Angiogenesis Process

摘要: Angiogenesis has been identified as an important target for antineoplastic therapy. The use of purine analogue antimetabolites in combination chemotherapy solid tumors proposed. To assess the possibility that selected analogues may affect tumor neovascularization, 6-methylmercaptopurine riboside (6-MMPR), 6-methylmercaptopurine, 2-aminopurine, and adenosine were evaluated capacity to inhibit angiogenesis vitro vivo. 6-MMPR inhibited fibroblast growth factor-2 (FGF2)-induced proliferation delayed repair mechanically wounded monolayer endothelial GM 7373 cell cultures. also formation sprouts within fibrin gel by FGF2-treated murine brain microvascular cells capillary-like structures on Matrigel aortic transfected with FGF2 cDNA. affected FGF2-induced intracellular signaling inhibiting phosphorylation extracellular signal-regulated kinase-2. other molecules ineffective all assays. In vivo, vascularization chick embryo chorioallantoic membrane prevented blood vessel induced human endometrial adenocarcinoma specimens grafted onto membrane. Also, topical administration caused regression newly formed vessels rabbit cornea. Thus, specifically inhibits both early late phases process exerts a potent anti-angiogenic activity These results provide new rationale therapy cancer.