Roles Of Cyclooxygenase-1 And -2 In Uv-induced Skin Canc

紫外线是人类接触到的主要环境因素之一，也是导致人类皮肤癌的重要原因。非甾体抗炎药（NSAIDs）可以减少人类和啮齿类动物的几种癌症。非甾体抗炎药被认为是通过抑制环氧化酶（COX）起作用的，我们已经观察到COX-1和COX-2缺乏在启动/促进模型中使小鼠皮肤乳头状瘤的形成减少了约80%，数据表明角化细胞分化的改变可能是原因。我们对紫外线的研究表明，与野生型小鼠相比，缺乏COX-2而非COX-1的小鼠表现出剂量依赖性的表皮皮肤损伤和细胞死亡增加。与COX-1缺失或野生型小鼠相比，COX-2缺失小鼠的细胞凋亡水平增加了约2倍。COX-2缺失小鼠从紫外线诱导的表皮损伤中恢复的速度也比野生型小鼠慢。

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.