Sinicrope Frank A
Division of Gastroenterology & Hepatology, Division of Oncology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Mol Carcinog. 2006 Jun;45(6):447-54. doi: 10.1002/mc.20232.
Cyclooxygenase-2 (COX-2) is an inducible enzyme that regulates prostaglandin synthesis and is overexpressed at sites of inflammation and in several epithelial cancers. A causal link for COX-2 in epithelial tumorigenesis was shown in genetically manipulated animal models of colon and breast carcinoma. Studies have elucidated the regulation of COX-2 expression and have identified EP receptors through which prostanoids exert their biological effects. Mechanistic studies indicated that COX-2 is involved in apoptosis resistance, angiogenesis, and tumor cell invasiveness, which appear to contribute to its effects in tumorigenesis. Furthermore, forced COX-2 expression has been shown to suppress apoptosis by modulating the level of death receptor 5 (DR5) and this effect was reversed by a COX inhibitor. COX enzymes are targets for cancer prevention as shown by the observation that nonselective COX and selective COX-2 inhibitors have been reported to effectively prevent experimental colon cancer and can regress colorectal polyps in patients with familial adenomatous polyposis. This review will focus on the role of COX-2 as a target for the prevention and treatment of human colorectal cancer.
环氧化酶-2（COX-2）是一种诱导性酶，可调节前列腺素的合成，在炎症部位和几种上皮癌中过度表达。在结肠癌和乳腺癌的基因操纵动物模型中显示了COX-2在上皮肿瘤发生中的因果关系。研究阐明了COX-2表达的调节，并确定了前列腺素发挥其生物学作用的EP受体。机制研究表明，COX-2参与抗凋亡、血管生成和肿瘤细胞侵袭，这些似乎都有助于其在肿瘤发生中的作用。此外，已证明强制表达COX-2可通过调节死亡受体5（DR5）的水平来抑制细胞凋亡，并且这种作用可被COX抑制剂逆转。如观察到非选择性COX和选择性COX-2抑制剂已被报道可有效预防实验性结肠癌并可使家族性腺瘤性息肉病患者的结直肠息肉消退所示，COX酶是癌症预防的靶点。本综述将聚焦于COX-2作为人类结直肠癌预防和治疗靶点的作用。
