Increased expression of cyclooxygenase (COX)-2 in DMBA-induced hamster cheek pouch carcinogenesis and chemopreventive effect of a selective COX-2 inhibitor celecoxib
Increased expression of cyclooxygenase (COX)-2 in DMBA-induced hamster cheek pouch carcinogenesis and chemopreventive effect of a selective COX-2 inhibitor celecoxib
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DOI：
10.1111/j.1600-0714.2004.00254.x
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发表时间：
2004-11-01
影响因子：
3.3
通讯作者：
Sakurai, K
中科院分区：
文献类型：
--
作者：
Nishimura, N;Urade, M;Sakurai, K
背景：近年来，有报道称环氧合酶（考克斯）-2蛋白和mRNA在多种肿瘤组织中过度表达。方法：用0.5%DMBA丙酮溶液涂抹金黄地鼠的颊囊，观察考克斯-2的表达情况。结果：免疫组化和Western blot分析显示，考克斯-2表达在肿瘤发生过程中呈上升趋势，而在肿瘤发生过程中，考克斯-2表达呈下降趋势。尽管所有仓鼠均发生鳞状细胞癌，但肿瘤形成的发生以剂量依赖性方式延迟。此外，塞来昔布治疗组的肿瘤生长迟缓，存活动物增加。从组织学上看，塞来昔布可增加肿瘤实质中的凋亡细胞，并显著抑制间质中的血管生成。结论：考克斯-2在仓鼠颊囊化学致癌过程中表达增加。塞来昔布的管理证明了对致癌的化学预防潜力。
BACKGROUND: In recent years, overexpression of cyclooxygenase (COX)-2 protein and mRNA has been reported in various cancer tissues. Therefore, it has been suggested that COX-2 is related to carcinogenesis.METHODS: Hamsters were treated by painting a buccal pouch with a 0.5% DMBA solution dissolved in acetone. Basal diet or diets containing 150, 500 and 1500 ppm of celecoxib, a selective COX-2 inhibitor, were given ad libitum to hamsters, and tumor development was observed.RESULTS: Immunohistochemical and Western blot analyses revealed that COX-2 expression was increased toward the carcinogenesis. Although all hamsters developed squamous cell carcinoma, the onset of tumor formation was delayed in a dose-dependent manner. Also, tumor growth was retarded and survived animals were increased in the group of celecoxib treatment. Histologically, administration of celecoxib increased the apoptotic cells in the tumor parenchyma and significantly inhibited the angiogenesis in the stroma.CONCLUSIONS: The COX-2 expression was increased during hamster cheek pouch chemical carcinogenesis. Administration of celecoxib demonstrated the chemopreventive potential against the carcinogenesis.