Cyclooxygenases (COX) catalyze the first rate-limiting steps in the conversion of arachidonic acid to prostaglaudins and thromboxanes. Two isoforms of this enzyme have been identified; COX-1 and COX-2. COX-1 is constitutively expressed and involvedin the modulation of normal physiologic systems such as the gastrointestinal tract, kidneys and platelets. COX-2 can be induced by growth factors, cytokines and tumor promoters and is paramount in the development of inflammation. More recently, researchhas shown COX-2 plays a significant role in the development and progression of cancer by converting procarcinogens to carcinogens. The production of prostaglandin E_2 by COX-2 has been linked to the promotion of tumorigenesis. COX-2 overexpression in cells will inhibit natural cell death (called apoptosis), allowing neoplastic cells to continue to thrive. Other mechanisms by which COX-2 contributes to tumor development include increased adhesion and invasiveness of cancer cells (allows for faster growthand cancer spread), increased cell growth, and suppression of the immune system, thereby enabling tumors to escape detection from the immune system and angiogenesis. Other studies have implicated COX-2 in the development of new blood vessels to the tumor (angiogenesis), which allows for tumor growth and metastasis.
展开▼
