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

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NSAID通过抑制环加氧酶（考克斯）起作用，并且我们已经观察到，在起始/促进模型中，考克斯-1和考克斯-2缺陷都使小鼠皮肤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的研究表明，与野生型小鼠相比，考克斯-2缺陷而非考克斯-1缺陷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倍。考克斯-2缺失小鼠也比野生型小鼠更慢地从UV诱导的表皮损伤中恢复。

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.