Roles Of Cyclooxygenase-1 and -2 In UV-induced Skin Canc

环氧合酶-1 和-2 在紫外线诱导的皮肤癌中的作用

• 批准号: 7168254
• 负责人: Robert Langenbach
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7168254
• 关键词: Roles; Cyclooxygenase; UV; induced; Skin

Epidemiological studies indicate that ultra violet (UV) radiation causes skin damage and is a major environmental agent in skin cancer development. The effects of COX-1 and COX-2 deficiency, as well as COX-1 and COX-2 selective inhibitors, in acute UV dose induced skin damage have been studied. The results indicate that mice deficient in COX-2, but not COX-1, exhibit dose dependent increases in epidermal skin damage and cell death compared to wild type mice. Levels of apoptosis were increased about 2.5 -fold in COX-2 null mice compared to COX-1 null or wild type mice. The prostaglandin E2 receptors, EP2 and EP4, have been demonstrated to be involved in COX-2's protective effect against UV induced skin damage. Furthermore, the signaling pathways activated by EP2 and EP4 in the protection of UVB induced skin damage have been partially elucidated, and shown to involve PKA and Akt, respectively.

流行病学研究表明，紫外线辐射会造成皮肤损伤，是皮肤癌发展的主要环境因素。研究了考克斯-1和考克斯-2缺乏以及考克斯-1和考克斯-2选择性抑制剂在急性UV剂量诱导的皮肤损伤中的作用。结果表明，与野生型小鼠相比，缺乏考克斯-2而非考克斯-1的小鼠表现出表皮皮肤损伤和细胞死亡的剂量依赖性增加。与考克斯-1缺失或野生型小鼠相比，考克斯-2缺失小鼠的细胞凋亡水平增加约2.5倍。前列腺素E2受体EP 2和EP 4已被证明参与考克斯-2对UV诱导的皮肤损伤的保护作用。此外，EP 2和EP 4激活的信号通路在UVB诱导的皮肤损伤的保护中已被部分阐明，并显示分别涉及PKA和Akt。