【摘要】 目的:分析和比较选择性环氧合酶-2 (Cox-2)抑制剂塞来昔布、5-脂氧合酶(5-Lox)抑制剂齐留通及Cox/5-Lox双酶抑制剂利克飞龙对酒精相关性口腔癌的抑制作用。方法:选择66只C57BL/6小鼠,分为阴性对照组、模型组(4NQO组)、阳性对照组、齐留通干预组、塞来昔布干预组和利克飞龙干预组。阴性对照组不做任何处理,其余各组饮用50μg/m L四硝基喹啉-1-氧化物(4NQO)溶液16周后,阳性对照组及各干预组以8%酒精溶液代替饮用水喂养8周,同时开始分别用三蒸水和同等药量的齐留通、塞来昔布、利克飞龙(100 mg·kg-1·d-1)灌胃8周;于24周处死动物,取舌行组织病理学观察、BrdU免疫组化染色、蛋白质印迹法(Western-blot)检测舌组织中5-Lox、Cox-2蛋白的表达。结果:饮用酒精后,口腔癌发生率从16.7%增加到58.3%,5-Lox、Cox-2蛋白表达显著增加癌组织中BrdU阳性率显著升高。齐留通干预后,口腔癌发生率(41.7%)显著降低,5-Lox表达显著减少,Cox-2表达显著增加,Brd U阳性率显著降低;塞来昔布干预后,口腔癌发生率(50.0%)显著降低,Cox-2表达显著减少,5-Lox表达显著增加,BrdU阳性率显著降低;利克飞龙干预后,口腔癌发生率(25%),Brd U阳性率与阳性对照组、齐留通干预组和塞来昔布干预组相比均显著降低,5-Lox、Cox-2蛋白表达比阳性对照组显著减少(P<0.05)。结论:酒精促进口腔癌变的过程可能与5-Lox和Cox-2的表达上调关系密切;齐留通和塞来昔布可以分别抑制5-Lox和Cox-2活性,使口腔癌的发生率显著降低;利克飞龙对口腔癌的抑制作用优于齐留通和塞来昔布。更多还原

【Abstract】 Objective: To study the inhibitory effect of Zileuton( a specific 5-Lox inhibitor),Celecoxib( a specific Cox-2 inhibitor) and Licofelone(a dual Cox/5-Lox inhibitor) on ethanol-related oral carcinogenesis in mice. Methods: 66 C57 BL/6 mice were divided into 6 groups randomly. The negative control group( n = 6) was not treated, the remaining mice were divided into 5 groups(12 mice in each group) and treated with 4 NQO in their drinking water at a concentration of 50 μg/m L for a period of 16 weeks. Then the mice in 4 NQO control group was not treated afterwards, those in the other 4 groups were received by distilled water, Zileuton, Celecoxib and Licofelone respectively. At week 24, all the animals were sacrificed. The tongue was harvested and examined for histopathology,immunohistochemical and western blotting. Results: Long-term 8% ethanol consumption significantly increased the oral SCC incidence(from 16.7% to 58.3%),5-Lox and Cox-2 protein expression, and the Brd U-labeling index The oral SCC incidence and the BrdU-labeling index in Zileuton group, Celecoxib group and Licofelone group were significantly lower than those in positive control group. The oral SCC incidence and the Brd U-labeling index in Licofelone group were significantly lower than those in Zileuton group or Celecoxib group. 5-Lox and Cox-2 protein expression in Licofelone group, 5-Lox protein expression in Zileuton group and Cox-2 protein expression in celecoxib group were significantly lower than those in positive control group. Cox-2 protein expression in Zileuton group and 5-Lox protein expression in Celecoxib group were significantly higher than those in positive control group. Conclusions:Ethanol can promot 4 NQO-induced oral carcinogenesis through activation of the 5-Lox and Cox-2 pathway of arachidonic acid metabolism. Zileuton and Celecoxib have inhibitory effects against ethanol-related oral carcinogenesis and such inhibition may be related to the suppression of 5-Lox and Cox-2 protein expression. The inhibitory effect of Licofelone is better than that of Zileuton and Celecoxib, and Licofelone may be potentially used for oral cancer prevention in the future.更多还原