Roles Of Cyclooxygenase-1 And -2 In UV-Induced Skin Canc

环加氧酶-1 和-2 在紫外线诱导的皮肤癌中的作用

• 批准号: 6546703
• 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/6546703
• 关键词: apoptosis; cancer prevention; carcinogenesis; environment related neoplasm /cancer; enzyme activity; enzyme deficiency; enzyme induction /repression; enzyme inhibitors; keratinocyte; laboratory mouse; light adverse effect; neoplastic growth; nonsteroidal antiinflammatory agent; prostaglandin endoperoxide synthase; prostaglandins; skin disorder chemotherapy; skin neoplasms; ultraviolet radiation

Ultraviolet light is one of the major environmental factors to which humans are exposed and is known to be a significant cause of human skin cancer. Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce several types of cancers in humans and rodents. NSAIDs are believed to act by inhibiting the cyclooxygenases (COX), and we have observed that both COX-1 and COX-2 deficiencies reduce mouse skin papilloma formation by about 80% in the initiation/ promotion model with the data suggesting that altered keratinocyte differentiation may be responsible. Our studies with UV 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-fold in COX-2 null mice compared to COX-1 null or wild type mice. The COX-2 null mice also recovered from the UV induced epidermal damage more slowly then did wild type mice.

紫外线是人类暴露的主要环境因素之一，被称为人类皮肤癌的重要原因。非甾体类抗炎药（NSAIDS）减少了人类和啮齿动物中的几种类型的癌症。据信NSAID可以通过抑制环氧合酶（COX）来起作用，并且我们观察到，在开始/促进模型中，COX-1和COX-2缺陷均减少了小鼠皮肤乳头状瘤的形成约80％，该数据表明改变角质形成细胞的差异可能会负责。我们对紫外线的研究表明，与野生型小鼠相比，表皮皮肤损伤和细胞死亡的剂量依赖性增加，而剂量依赖性增加。与COX-1无效或野生型小鼠相比，COX-2无效小鼠的凋亡水平升高约2倍。 COX-2 NULL小鼠还从紫外线诱导的表皮损伤中恢复了更慢，然后野生型小鼠。