Reduction of UV-induced skin tumors in hairless mice by selective COX-2 inhibition
Reduction of UV-induced skin tumors in hairless mice by selective COX-2 inhibition
复制标题
DOI：
10.1093/carcin/20.10.1939
复制
发表时间：
1999-10-01
期刊：
影响因子：
4.7
通讯作者：
Han, RJ
中科院分区：
文献类型：
--
作者：
Pentland, AP;Schoggins, JW;Han, RJ
紫外光是一种完全的致癌物质，可诱导基底细胞和鳞状细胞皮肤癌。该研究使用选择性COX-2抑制剂塞来昔布（celecoxib）来检测COX-2抑制在减少紫外光诱导的无毛小鼠皮肤肿瘤形成中的功效。选择UVA-340太阳灯作为光源，有效地模仿太阳的UVA和UVB光谱。无毛小鼠每周照射5天，总剂量为2.62 J/cm(2)。当90%的小鼠至少有一个肿瘤时，将小鼠分为两组，使肿瘤数量和多重性相同（P < 0.31）。然后给一半的小鼠喂食含有1500ppm塞来昔布的饮食。观察10周后肿瘤的数量、多样性和大小。95%形成的肿瘤经组织病理学评估为鳞状细胞癌，肿瘤中COX-2的表达和活性增加。10周后，药物治疗组肿瘤数量和多样性的差异是紫外线对照组的56% （P < 0.001）。结果表明，口服选择性COX-2抑制剂塞来昔布可防止光致癌发生后新肿瘤的形成，表明塞来昔布治疗可能对预防紫外线诱导的人类皮肤肿瘤非常有用。
UV light is a complete carcinogen, inducing both basal and squamous cell skin cancers, The work described uses the selective COX-2 inhibitor celecoxib to examine the efficacy of COX-2 inhibition in the reduction of UV light-induced skin tumor formation in hairless mice. UVA-340 sun lamps were chosen as a light source that effectively mimics the solar UVA and UVB spectrum. Hairless mice were irradiated for 5 days a week for a total dose of 2.62 J/cm(2). When 90% of the animals had at least one tumor, the mice were divided into two groups so that the tumor number and multiplicity were the same (P < 0.31). Half of the mice were then fed a diet containing 1500 p.p.m. celecoxib. Tumor number, multiplicity and size were then observed for the next 10 weeks. Ninety-five percent of the tumors formed were histopathologically evaluated as squamous cell carcinoma, COX-2 expression and activity were increased in tumors. After 10 weeks, the difference in tumor number and multiplicity in the drug-treated group was 56% of UV controls (P < 0.001), The results show that the orally administered selective COX-2 inhibitor celecoxib prevents new tumor formation after the onset of photocarcinogenesis and suggest that treatment with celecoxib may be very useful in preventing UV-induced skin tumors in humans.