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

环氧合酶2抑制剂治疗口腔癌的实验研究

• 批准号: 14571904
• 负责人: YAMAMOTO Kazuhiko
• 金额: $ 2.18万
• 依托单位: Nara Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571904/
• 关键词: cyclooxygenase-2; etodolac; 4-nitroquinoline 1-oxide; tongue cancer; rat; chemoprevention; nitric oxide synthase; nimesulide; 4-nitroquinoline 1--oxide; oral cancer

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.

我们分析了选择性环氧合酶 (COX)-2 抑制剂尼美舒利和依托度酸在使用 4-硝基喹啉 1-氧化物 (4-NQO) 的大鼠舌癌模型中的功效，以评估它们对人类口腔癌的化学预防效果，并报告这些抑制剂对鳞状细胞癌 (SCC) 和鳞状细胞斑点（假定的癌前病变）发展的抑制作用病变。本研究旨在阐明 COX-2 在大鼠舌癌发生中的作用。给大鼠注射 4-NQO (25-35 ppm) 12 周，然后给予依托度酸 (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COX-2和诱导型一氧化氮合酶（iNOS）的免疫组化表达。剂量为 300ppm 的依托度酸可将鳞状细胞癌的发生率从 100% 显着抑制至 50%，同时异型增生的发生率也会增加。 SCC 的尺寸也减小了。这些结果表明依托度酸抑制了不典型增生向鳞状细胞癌的进展以及鳞状细胞癌的增殖潜力。对COX-2和iNOS表达的免疫组织化学研究表明，依托度酸对COX-2和iNOS的表达没有影响。从这些结果可以认为，依托度酸对SCC发展的抑制作用不是通过抑制COX-2蛋白表达来发挥的，而是通过抑制COX-2的酶活性来发挥的。

项目成果

Kazuhiko Yamamoto, Wakashi kitayama, Ayumi Denda, Ayumu Morisaki, Hiroki Kuniyasu, Tadaaki Kirita: "Inhibitory effects of selective cyclooxygenase-2 inhibitors, nimesulide and etodolac, on the development of squamous cell dysplasias and carcinomas in the

Kazuhiko Yamamoto、Wakashi kitayama、Ayumi Denda、Ayumu Morisaki、Hiroki Kuniyasu、Tadaaki Kirita：“选择性环氧合酶 2 抑制剂尼美舒利和依托度酸对鳞状细胞发育不良和癌症发展的抑制作用

Kazuhiko Yamamoto et al.: "Inhibitory effects of selective cyclooxygenase-2 inhibitors, nimesulide and etodolac, on the development of squamous cell dysplasias and carcinomas of the tongue in rats initiated with 4-nitroquinoline 1-oxide"Cancer Letter. 199

Kazuhiko Yamamoto 等人：“选择性 cyclooxygenase-2 抑制剂尼美舒利和依托度酸对 4-硝基喹啉 1-氧化物引发的大鼠鳞状细胞发育不良和舌癌发展的抑制作用”《癌症信》。