Multiple roles of COX-2 in tumor angiogenesis: a target for antiangiogenic therapy

摘要: Abstract Angiogenesis is required for multistage carcinogenesis. The inducible enzyme cyclooxygenase-2 (COX-2) an important mediator of angiogenesis and tumor growth. COX-2 expression occurs in a wide range preneoplastic malignant conditions; the has been localized to neoplastic cells, endothelial immune stromal fibroblasts within tumors. proangiogenic effects are mediated primarily by three products arachidonic metabolism: thromboxane A2 (TXA2), prostaglandin E2 (PGE2), I2 (PGI2). Downstream actions these eicosanoid include: (1) production vascular growth factor; (2) promotion sprouting, migration, tube formation; (3) enhanced cell survival via Bcl-2 Akt signaling; (4) induction matrix metalloproteinases; (5) activation epidermal factor receptor-mediated angiogenesis; (6) suppression interleukin-12 production. Selective inhibition activity shown suppress vitro vivo. Because agents safe well tolerated, selective inhibitors could have clinical utility as antiangiogenic cancer prevention, intervention established disease alone or combination with chemotherapy, radiation, biological therapies.