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，并且已知是人类皮肤癌的重要原因。 非甾体抗炎药（NSAID）可减少人类和啮齿动物的几种癌症。据信非甾体抗炎药通过抑制环加氧酶（考克斯）发挥作用，我们观察到，在启动/促进模型中，考克斯-1和考克斯-2缺陷均可使乳头状瘤形成减少约80%，数据表明角质形成细胞分化的改变可能是原因。我们对UV的初步研究表明，考克斯-2缺陷而非考克斯-1缺陷的小鼠表现出凋亡的剂量依赖性增加，与考克斯-1缺失或野生型相比，其高达5倍 小鼠，并且这种增加的凋亡可能导致降低的致瘤反应。