Roles of cyclooxygenase 1 & 2 in UV induced skin cancer

紫外线是人类暴露在其中的主要环境因素之一，众所周知，紫外线是人类皮肤癌的重要原因。非类固醇抗炎药(NSAIDs)可以减少人类和啮齿动物的几种癌症。非甾体抗炎药被认为是通过抑制环氧合酶(COX)发挥作用的，我们观察到COX-1和COX-2的缺陷在启动/促进模型中减少了约80%的乳头状瘤形成，数据表明角质形成细胞分化的改变可能是原因之一。我们的紫外线初步研究表明，缺乏COX-2而不是COX-1的小鼠表现出剂量依赖性的凋亡增加，与COX-1缺失或野生型相比高达5倍 这种增加的细胞凋亡率可能会导致肿瘤发生反应的降低。

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.