Studies on the involvement of inflammatory stimuli and immortalization of cells in tongue carcinogenesis and cancer chemoprevention

炎症刺激和细胞永生化参与舌癌发生和癌症化学预防的研究

• 批准号: 10671782
• 负责人: TANAKA Takuji
• 金额: $ 1.98万
• 依托单位: Kanazawa 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: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671782/
• 关键词: Tongue carcinogenesis; Inhibition of carcinogenesis; Nimesulide; COX-2 inhibitor; COX-2; 牛ラクトフェリン; フラボノイド; モリン; 炎症性刺激; 発がん阻止; 抗酸化作用

Our previous study indicated that expression of COX-2 protein involves in 4-NQO-induced rat tongue carcinogenesis. In this year, therefore, we investigated possible modifying effect of nimesulide, which specific inhibitor of COX-2, on 4-NQO-induced rat tongue tumorigenesis.A total of 97 male F344 rats aged 4 weeks were used. Rats were given 4-NQO (20 ppm in drinking water) for 8 weeks to induced tongue squamous cell carcinoma. They were also fed the diets mixed w* nimesulide at a dose of 0.01% or 0.04% during the initiation (10 weeks) or promotion phase (22 weeks). The experiment was terminated 32 weeks after the start. At the end of the study, the incide* of tongue squamous cell carcinoma were 48% (13/27 rats) in the 4-NQO alone group, 20% (3/15 rats) in 4-NQO+0.01% nimesulide group, 13% (2/15 rats) in the 4-NQO+0.04% nimesulide group, 42% (5/12 rats) in the 4-NQO→0.01% nimesulide group, and 8% (1/12 rats) in the 4-NQO→0.04% nimesulide group. Thus, feeding of nemesulide during either the initiation or promotion pahse *tumorirgenesis significantly inhibited the development of tongue carcinoma (P<0.05). No tongue tum* were present in rats of nimesulide alone (0.04%) and untreated control. These results suggest that a COX-2 sepcific inhibitor nimesulide is applicable for human clinical trial for chemoprevention of tongue cancer. The studies on mechanisms of inhibition are ongoing in our laboratory.It is well known that the treatment of 4-NQO in drinking water specifically prodeces tongue neoplas* However, in the present study, 4-NQO exposure induced squamous cell carcinoma in the palate and gi*of the maxilla as well as tongue carcinoma. Feeding of nimesulide also inhibited the development of th*tumors.

我们前期的研究表明COX-2蛋白的表达参与了4-NQO诱导的大鼠舌癌的发生。因此，今年我们研究了COX-2特异性抑制剂尼美舒利对4-NQO诱导的大鼠舌肿瘤发生的可能调节作用。总共使用97只4周龄的雄性F344大鼠。给大鼠注射 4-NQO（20 ppm 饮用水）8 周，诱导舌鳞状细胞癌。在起始阶段（10 周）或促进阶段（22 周），他们还喂食混合有 0.01% 或 0.04% 尼美舒利的饮食。实验在开始后 32 周终止。研究结束时，舌鳞状细胞癌的发生率*，4-NQO单独组为48%（13/27只大鼠），4-NQO+0.01%尼美舒利组为20%（3/15只大鼠），4-NQO+0.04%尼美舒利组为13%（2/15只大鼠），4-NQO+0.04%尼美舒利组为42%（5/12只大鼠）。 4-NQO→0.01%尼美舒利组，4-NQO→0.04%尼美舒利组为8%(1/12大鼠)。因此，在肿瘤发生的起始阶段或促进阶段喂食奈美舒利可显着抑制舌癌的发展（P<0.05）。单独使用尼美舒利 (0.04%) 的大鼠和未经治疗的对照大鼠均未出现舌肿*。这些结果表明COX-2特异性抑制剂尼美舒利适用于舌癌化学预防的人体临床试验。我们的实验室正在进行有关抑制机制的研究。众所周知，饮用水中的 4-NQO 处理特别会导致舌肿瘤*。然而，在本研究中，4-NQO 暴露会诱发上颚和上颌骨的鳞状细胞癌以及舌癌。尼美舒利的喂养也抑制了肿瘤的发展。

项目成果

Takuji Tanaka, Hiroyuki Kohno, Shin-ichiro Yoshitani, Shigeki Takashima, Ataru okumura, Akira Murakami, and Masashi Hosokawa: "Ligands for peroxisome proliferator-activated receptor α and γ inhibit chemically-induced colitis and formation of aberrant cryp

Takuji Tanaka、Hiroyuki Kohno、Shin-ichiro Yoshitani、Shigeki Takashima、Ataru okumura、Akira Murakami 和 Masashi Hosokawa：“过氧化物酶体增殖物激活受体 α 和 γ 的配体抑制化学诱导的结肠炎和异常哭声的形成

Takuji Tanaka, Kunihiro Kawabata, Hiroyuki Kohno, Shiro Honjo, Manabu Murakami, Reona Shimada, Seiko Kagami, and Hiroyuki Tsuda: "Bovine lactoferrin inhibits rat tongue carcinogenesis."Lactoferrin : Structure, Function and Applications, Elvesier Sci., Ams

Takuji Tanaka、Kunihiro Kawabata、Hiroyuki Kohno、Shiro Honjo、Manabu Murakami、Reona Shimada、Seiko Kagami 和 Hiroyuki Tsuda：“牛乳铁蛋白抑制大鼠舌头癌变。”乳铁蛋白：结构、功能和应用，Elvesier Sci.，Ams

Murakami,A., et al.: "Inhibitory effect of citrus nobiletin on phorbol ester-induced skin inflammation, oxidative stress, and tumor promotion in mice"Cancer Research. 60・18. 5059-5066 (2000)

Murakami, A., et al.：“柑橘川陈皮素对佛波酯诱导的小鼠皮肤炎症、氧化应激和肿瘤促进的抑制作用”癌症研究 60·18 (2000)。

Kawabata,K., et al.: "Suppression of N-nitrosomethylbenzylamine-induced rat esophageal tumorigenesis by dietary feeding of 1'-acetoxychavicol acetate"Japanese Journal of Cancer Research. 91・2. 148-155 (2000)

Kawabata, K., et al.：“通过膳食喂养 1-乙酰氧基胡椒酚乙酸酯抑制 N-亚硝基甲基苄胺诱导的大鼠食管肿瘤发生”，日本癌症研究杂志 91·2（2000 年）。

Murakami,A., et al.: "Inhibitory effect of citrus nobiletin on phorbol ester-induced skin inflammation, oxidative stress, and tumor promotion in mice"Cancer Research. 61・18. 5059-5066 (2000)

Murakami, A., et al.：“柑橘川陈皮素对佛波酯诱导的小鼠皮肤炎症、氧化应激和肿瘤促进的抑制作用”癌症研究 61·18 (2000)。