Inhibitory effects of troglitazone, a peroxisome proliferator-activated receptor γ ligand, in rat tongue carcinogenesis initiated with 4-nitroquinoline 1-oxide
Inhibitory effects of troglitazone, a peroxisome proliferator-activated receptor γ ligand, in rat tongue carcinogenesis initiated with 4-nitroquinoline 1-oxide
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DOI：
10.1111/j.1349-7006.2003.tb01448.x
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发表时间：
2003-04-01
期刊：
影响因子：
5.7
通讯作者：
Mori, H
中科院分区：
文献类型：
--
作者：
Yoshida, K;Hirose, Y;Mori, H
过氧化物酶体增殖物激活受体（PPAR）γ的配体与某些恶性肿瘤的生长抑制和细胞分化有关。在这项研究中，在雄性F344大鼠中研究了在4-硝基喹啉1-氧化物（4-NQO）引发的口腔癌发生后起始阶段给予曲格列酮（一种PPARgamma配体）的作用。给6周龄的大鼠以20 ppm的剂量给予4-NQO 8周以诱发舌肿瘤。从4-NQO暴露停止后1周开始，动物喂食含0、30或100 ppm曲格列酮的饲料，持续22周。在研究结束时（第32周），4-NQO诱导的舌肿瘤和癌前病变的发生率进行了组织病理学测定，并通过计数溴脱氧尿苷（BrdU）标记指数和细胞周期蛋白D1阳性细胞比率估计细胞增殖活性。此外，免疫组化表达环氧合酶（考克斯）-2和PPARgamma的舌病变进行了评估。与未给予曲格列酮治疗组相比，给予100 ppm曲格列酮喂养可显著降低鳞状细胞癌的发病率（5.0% vs. 45.8%，P
Ligands for peroxisome proliferator-activated receptor (PPAR) gamma have been implicated in growth inhibition and cell differentiation in certain malignancies. In this study, the effects of troglitazone, a PPARgamma ligand, given during the postinitiation phase of oral carcinogenesis initiated with 4-nitroquinoline 1-oxide (4-NQO) were investigated in male F344 rats. Rats aged 6 weeks were given 4-NQO at 20 ppm for 8 weeks to induce tongue neoplasms. Starting 1 week after the cessation of 4-NQO exposure, animals were fed diets containing 0, 30 or 100 ppm troglitazone for 22 weeks. At the end of the study (week 32), the incidences of 4-NQO-induced tongue neoplasms and preneoplasms were determined histopathologically and cell proliferation activity was estimated by counting bromodeoxyuridine (BrdU)-labeling indices and cyclin D1-positive cell ratios. In addition, immunohistochemical expression of cyclooxygenase (COX)-2 and PPARgamma was assessed in the tongue lesions. Feeding with 100 ppm troglitazone significantly decreased the incidence of squamous cell carcinoma when compared to the group without troglitazone treatment (5.0% vs. 45.8%, P