Experimental study on therapy for oral cancer by cyclooxygenase-2 inhibitors

我们分析了选择性环氧合酶（考克斯）-2抑制剂尼美舒利和依托度酸的疗效，在大鼠舌癌模型中使用4-硝基喹啉1-氧化物（4-NQO），以评估其对人类口腔癌的化学预防效果，并报告了这些抑制剂对鳞状细胞癌（SCC）和鳞状细胞daplasias（假定的癌前病变）的发展的抑制作用。本研究旨在探讨考克斯-2在大鼠舌癌发生中的作用。给大鼠4-NQO（25-35 ppm）12周，然后给依托度酸（150 ppm和300 ppm）16周。分析依托度酸对肿瘤和癌前病变发生率的影响以及这些病变中考克斯-2和诱导型一氧化氮合酶（iNOS）的免疫组化表达。依托度酸300 ppm剂量组SCC发生率从100%降至50%，与此同时异型增生发生率增加。SCC的大小也减少。这些结果表明依托度酸抑制了发育不良向SCC的进展和SCC的增殖潜力。免疫组化检测考克斯-2和iNOS的表达，依托度酸对考克斯-2和iNOS的表达无影响。根据这些结果，认为依托度酸对SCC发展的抑制作用不是通过抑制考克斯-2蛋白表达，而是通过抑制考克斯-2的酶活性来发挥的。

We analyzed the efficacy of selective cyclooxygense(COX)-2 inhibitors, nimesulide and etodolac, in the rat model of tongue carcinogenesis using 4-nitroquinoline 1-oxide(4-NQO) in order to evaluate their chemopreventive efficacy on human oral cancers and reported the suppressive effect of these inhibitors on the development of squamous cell carcinomas(SCCs) and squamous cell daplasias, putative preneoplastis lesions. The present study was conducted to elucidate the roles of COX-2 in rat tongue carcinogenesis. Rats were administered 4-NQO (25-35 ppm) for 12 weeks and then etodolac (150ppm and 300ppm) was given for 16 weeks. The effect of etodolac on the incidence of neoplastic and preneoplastic lesions and the immunohistochemical expression of COX-2 and inducible nitoric oxide synthase (iNOS) in these lesions were analyzed. Etodolac at the dose of 300ppm significantly suppressed the incidence of SCCs from 100% to 50% in parallel with the increase of the incidence of dysplasias. The size of SCCs was also decreased. These results indicate that etodolac suppressed the progression of dysplasias to SCCs and the proliferative potential of SCCs. Immunohistochemical study on the expression of COX-2 and iNOS revealed that etodolac had no effect on the expression of COX-2 or iNOS. From these results, it is considered that the suppressive effect of etodolac on the development of SCCs was not exerted by the inhibition of COX-2 protein expression but by the inhibition of the enzymatic activity of COX-2.