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，考克斯-2蛋白的表达参与了4-NQO诱导的大鼠舌癌的发生。本研究采用考克斯-2（COX-2）特异性抑制剂尼美舒利（nimesulide）对4-NQO诱导的大鼠舌癌发生的影响。用4-NQO（20 ppm饮水）连续8周诱发大鼠舌鳞状细胞癌。在启动期（10周）或促进期（22周），他们还以0.01%或0.04%的剂量喂食混合有尼美舒利的饮食。实验在开始后32周终止。研究结束时，舌鳞癌的发生率为48%在4-NQO单独给药组中（13/27只大鼠），20% 4-NQO+0.01%尼美舒利组（3/15只），13%（13/15只）4-NQO+0.04%尼美舒利组为2/15，4-NQO→0.01%尼美舒利组为42%（5/12），4-NQO →0.04%尼美舒利组为8%（1/12）。在舌癌发生的起始期和促进期给予奈美舒利均能显著抑制舌癌的发生（P<0.05）。尼美舒利单独给药组（0.04%）和未给药对照组大鼠均未出现舌质 *。提示考克斯-2特异性抑制剂尼美舒利可用于舌癌化学预防的临床研究。众所周知，饮用水中的4-NQO处理特异性地诱发舌肿瘤。然而，在本研究中，4-NQO暴露诱发上颌骨的腭和GI的鳞状细胞癌以及舌癌。喂饲尼美舒利也能抑制th* 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)。