Experimental study on chemoprevention of oral cancer by cyclooxygenase-2 inhibitor

环氧合酶2抑制剂化学预防口腔癌的实验研究

• 批准号: 16592011
• 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: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16592011/
• 关键词: 4-nitroquinoline 1-oxide; etodolac; cyclooxygenase-2; chemoprevention; tongue cancer; rat; receptor for advanced glycation end products; receptor for advanced glycation end products; nimesulide

We analyzed the effect of a selective cyclooxygenase (COX)-2 inhibitors, etodolac, on the expression of COX-2 and receptor for advanced glycation end products (RAGE) in the rat model of tongue carcinogenesis using 4-nitroquinoline 1-oxide (4-NQO).Fischer 344 rats, 6-week-old, were administered 4-NQO (30ppm) for 12 weeks and then etodolac (150ppm and 300ppm) was given for 16 weeks. The lesions developed were histologically classified into hyperplasia, dysplaisa, pappiloma and squamous cell carcinoma (SCC).The incidence of SCC was decreased significantly by 300ppm etodolac. Immunohistochemically, COX-2 was positive for basal cells in hyperplasia and papilloma, and for basal cells, dysplastic cell and cancer cells in dysplasia and SCC. On the other hand, RAGE was weakly and moderately positive for granular cells in hyperplasia and papilloma, and positive for dysplastic cells and cancer cells in dysplasia and SCC. Etodolac did not decrease the expression of COX-2 in these lesions but decreased the expression of RAGE. The analysis of RAGE mRNA using RT-PCR revealed that RAGE mRNA was expressed in SCC and the treatment by etodolac decreased the expression.These results indicate that the expression of COX-2 and RAGE is closely related and the inhibitory effect by etodolac is associated with the decrease of RAGE mRNA expression in rat tongue carcinogenesis by 4-NQO.

我们利用4-硝基喹啉1-氧化物（4-NQO）分析了选择性环氧化酶(COX)-2抑制剂乙度酸对舌癌大鼠模型中COX-2和晚期糖基化终产物受体（RAGE）表达的影响。Fischer 344大鼠，6周龄，给予4-NQO (30ppm) 12周，然后给予依托度酸（150ppm和300ppm） 16周。病变在组织学上分为增生、发育不良、乳头状瘤和鳞状细胞癌。300ppm依托多拉酸可显著降低SCC的发生率。免疫组织化学结果显示，COX-2在增生和乳头状瘤的基底细胞中呈阳性，在发育不良和SCC的基底细胞、发育不良细胞和癌细胞中呈阳性。另一方面，RAGE在增生和乳头状瘤的颗粒细胞中呈弱、中阳性，在发育不良和鳞状细胞癌的发育不良细胞和癌细胞中呈阳性。依托度酸没有降低这些病变中COX-2的表达，但降低了RAGE的表达。RT-PCR分析RAGE mRNA，发现RAGE mRNA在SCC中有表达，依托多拉酸降低了RAGE mRNA的表达。这些结果表明COX-2与RAGE的表达密切相关，依托度酸的抑制作用与4-NQO对大鼠舌癌中RAGE mRNA表达的降低有关。

项目成果

Significance of expression of RAGE (receptor for advanced glycation end products) in oral squamous cell carcinoma.

RAGE（晚期糖基化终末产物受体）在口腔鳞状细胞癌中表达的意义。

• 发表时间: 2004
• 期刊: Japanese Journal of Head and Neck Cancer 30(4)
• 作者: Tomonori Sasahira;Tadaaki Kirita;Kazuhiko Yamamoto;Hiroki Kuniyasu
• 通讯作者: Hiroki Kuniyasu

Suppressive effects of a selective cyclooxygenase-2 inhibitor, etodolac, on 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis.

选择性环氧合酶 2 抑制剂依托度酸对 4-硝基喹啉 1-氧化物诱导的大鼠舌癌的抑制作用。

• 发表时间: 2004
• 期刊: Experimental and Toxicologic Pathology 56(3)
• 作者: Kazuhiko Yamamoto;Wakashi Kitayama;Ayumi Denda;Ayumu Morisaki;Hiroki Kuniyasu;Masahide Inoue;Tadaaki Kirita
• 通讯作者: Tadaaki Kirita

Suppressive effects of a selective cyclooxygenase-2 inhibitor, etodolac, on 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis

选择性环氧合酶 2 抑制剂依托度酸对 4-硝基喹啉 1-氧化物诱导的大鼠舌癌的抑制作用

• 发表时间: 2004
• 期刊: Experimental and Toxicologic Pathology 56(3)
• 作者: Kazuhiko Yamamoto;et al.
• 通讯作者: et al.

口腔扁平上皮癌におけるReceptor for Advanced Glycation End Products (RAGE) 発現の意義

• DOI: 10.5981/jjhnc.30.646
• 发表时间: 2004
• 作者: 智則 笹平;忠昭 桐田;一彦 山本;弘基 國安