Roles of cyclooxygenase 1 & 2 in UV induced skin cancer

环氧合酶 1 的作用

• 批准号: 6413337
• 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/6413337
• 关键词: apoptosis; cancer prevention; environment related neoplasm /cancer; laboratory mouse; neoplastic growth; nonsteroidal antiinflammatory agent; prostaglandin endoperoxide synthase; prostaglandins; 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 papilloma formation by about 80% in the initiation/ promotion model with the data suggesting that altered keratinocyte differentiation may be responsible. Our preliminary studies with UV indicate that mice deficient in COX-2, but not COX-1, exhibit dose dependent increases in apoptosis which are up to 5-fold elevated compared to COX-1 null or wild type mice and that this increased apoptosis could result in a reduced tumorigenic response.

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，我们已经观察到，在起始/促进模型中，COX-1和COX-2缺陷均通过数据表明改变角质形成细胞分化的数据可能负责。我们使用紫外线的初步研究表明，与COX-1 NULL或野生型相比，缺乏COX-2但不足COX-1的小鼠表现出剂量依赖性增加，高达5倍 小鼠和这种增加的细胞凋亡可能导致致瘤反应降低。