Studies on the involvement of peroxisome-proliferator activated receptor in rat tongue carcinogenesis and inhibition by their ligands

过氧化物酶体增殖物激活受体参与大鼠舌癌发生及其配体抑制作用的研究

• 批准号: 13671986
• 负责人: TANAKA Takuji
• 金额: $ 1.92万
• 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: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671986/
• 关键词: PPAR; Ligand; Tongue carcinogenesis; 4-NQO; Chemoprevention; Rats; 発がん防御; 舌がん培養株; 増殖抑制; 細胞周期修飾; アポトーシス

The present study was conducted to investigate the possible involvement of PPAR expression during tongue carcinogenesis and the chemopreventive ability of PPAR ligands against tongue tumorigenesis in rats. The results obtained are as follows :1) The human tongue cancer cell lines HCS-2 and NA expressed PPARγ and the expression of NA was greater than HCS-2.2) The growth of HCS-2 was inhibited by adding at high doses (40-50 μM) of a PPARγ ligand troglitazone and that of NA was inhibited dose-dependently by adding of troglitazone. FCM analysis revealed that troglitazone caused G1 arrest and apoptosis in both cell lines. The treatment also induced COX-2 expression.3) Dietary troglitazone (100 ppm) significantly inhibited 4-NQO-induced rat tongue carcinogenesis.4) Rat tongue squamous cell carcinoma induced by 4-NQO did not have β-catenin mutation.5) Dietary silymarin, which is an antioxidant and an inhibitor of arachidonic acid cascade, inhibited 4-NQO-induced rat tongue carcinogenesis through inhibition of cell proliferation and PGE2 biosynthesis.6) Apoptosis inducers capsaicin and rotenone from plants inhibited 4-NQO-induced rat tongue carcinogenesis through inhibition of cell proliferation and induction of Phase II drug metabolizing enzymes.

本研究旨在探讨过氧化物酶体增殖物激活受体（PPAR）在大鼠舌癌发生过程中的表达及其配体对舌癌发生的化学预防作用。结果表明：（1）人舌癌细胞株HCS-2和NA均表达PPARγ，且NA的表达量高于HCS-2。（2）高剂量（40-50 μM）的PPARγ配体曲格列酮可抑制HCS-2的生长，而曲格列酮则呈剂量依赖性抑制NA的生长。流式细胞仪分析表明，曲格列酮引起G1期阻滞和细胞凋亡。治疗还诱导了考克斯-2的表达。3）饮食曲格列酮（100 ppm）显著抑制4-NQO诱导的大鼠舌癌发生。4）由4-NQO诱导的大鼠舌癌没有β-连环蛋白突变。5）饮食水飞蓟素，这是一种抗氧化剂和花生四烯酸级联反应的抑制剂，通过抑制细胞增殖和PGE 2的生物合成，抑制4-NQO诱导的大鼠舌癌的发生。通过抑制细胞增殖和诱导II相药物代谢酶诱导大鼠舌癌发生。

项目成果

Hiroyuki Kohno, Masayo Maeda, Mikio Tanino, Yoshiaki Tsukio, Naomi Ueda, Keiji Wada, Shigeyuki Sugie, Hideki Mori, and Takuji Tanaka: "A bitter diterpenoid furanolactone columbin from Calumbae Radix inhibits azoxymethane-induced rat colon carcinogenesis"C

Hiroyuki Kohno、Masayo Maeda、Mikio Tanino、Yoshiaki Tsukio、Naomi Ueda、Keiji Wada、Shigeyuki Sugie、Hideki Mori 和 Takuji Tanaka：“天牛根中的苦味二萜呋喃内酯可抑制氧化偶氮甲烷诱导的大鼠结肠癌”C

Hiroyuki Kohno, Kazue Yamaguchi, Miki Taima, and Takuji Tanaka: "Prevention of colonic aberrant crypt foci by dietary feeding of chalcone and 2-hydroxychalcone in male F344 rats"J. Toxicol. Pathol.. 15. 137-143 (2002)

Hiroyuki Kohno、Kazue Yamaguchi、Miki Taima 和 Takuji Tanaka：“通过在雄性 F344 大鼠中饲喂查尔酮和 2-羟基查尔酮来预防结肠异常隐窝病灶”J.

Yasuhiro Yamada, Kazuya Hata, Yoshinobu Hirose, Akira Hara, Shigeyuki Sugie, Toshiya Kuno, Naoki Yoshimi, Takuji Tanaka, and Hideki Mori: "Microadenomatous lesions involving loss of Apc heterozygosity in the colon of adult ApcMin/+ mice"Cancer Res.. 62. 6

Yasuhiro Yamada、Kazuya Hata、Yoshinobu Hirose、Akira Hara、Shigeyuki Sugie、Toshiya Kuno、Naoki Yoshimi、Takuji Tanaka 和 Hideki Mori：“涉及成年 ApcMin/ 小鼠结肠中 Apc 杂合性缺失的微腺瘤病变”Cancer Res.. 62

Shin-ichiro Yoshitani, Takuji Tanaka, Hiroyuki Kohno, and Shigeki Takashima: "Chemoprevention of azoxymethane-induced rat colon carcinogenesis by dietary capsaicin and rotenone"Int. J. Oncol.. 19. 929-939 (2001)

Shin-ichiro Yoshitani、Takuji Tanaka、Hiroyuki Kohno 和 Shigeki Takashima：“通过膳食辣椒素和鱼藤酮化学预防氧化偶氮甲烷诱导的大鼠结肠癌”Int。

Hiroyuki Kohno, Takuji Tanaka, Kunihiro Kawabata, Yoshinobu Hirose, Shigeyuki Sugie, Hiroyuki Tsuda, and Hideki Mori: "Silymarin, a naturally occurring polyphenolic antioxidant flavonoid, inhibits azoxymethane-induced colon carcinogenesis in male F344 rat

Hiroyuki Kohno、Takuji Tanaka、Kunihiro Kawabata、Yoshinobu Hirose、Shigeyuki Sugie、Hiroyuki Tsuda 和 Hideki Mori：“水飞蓟素是一种天然存在的多酚抗氧化剂黄酮类化合物，可抑制雄性 F344 大鼠中氧化偶氮甲烷诱导的结肠癌发生