Suzuki Shugo, Mori Yukiko, Nagano Aya, Naiki-Ito Aya, Kato Hiroyuki, Nagayasu Yuko, Kobayashi Mizuho, Kuno Toshiya, Takahashi Satoru
Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
Pathology Division, Nagoya City East Medical Center, Nagoya 464-8547, Japan.
Int J Mol Sci. 2016 Dec 10;17(12):2071. doi: 10.3390/ijms17122071.
Pioglitazone (PGZ), a peroxisome proliferator-activated receptor γ agonist, which is known as a type 2 diabetes drug, inhibits cell proliferation in various cancer cell lines, including prostate carcinomas. This study focused on the effect of PGZ on prostate carcinogenesis using a transgenic rat for an adenocarcinoma of prostate (TRAP) model. Adenocarcinoma lesions as a percentage of overall lesions in the ventral prostate were significantly reduced by PGZ treatment in a dose-dependent manner. The number of adenocarcinomas per given area in the ventral prostate was also significantly reduced by PGZ treatment. The Ki67 labeling index in the ventral prostate was also significantly reduced by PGZ. Decreased cyclin D1 expression in addition to the inactivation of both p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)κB were detected in PGZ-treated TRAP rat groups. In LNCaP, a human androgen-dependent prostate cancer cell line, PGZ also inhibited cyclin D1 expression and the activation of both p38 MAPK and NFκB. The suppression of cultured cell growth was mainly regulated by the NFκB pathway as detected using specific inhibitors in both LNCaP and PC3, a human androgen-independent prostate cancer cell line. These data suggest that PGZ possesses a chemopreventive potential for prostate cancer.
吡格列酮（PGZ）是一种过氧化物酶体增殖物激活受体γ激动剂，作为一种2型糖尿病药物而闻名，它能抑制包括前列腺癌在内的多种癌细胞系中的细胞增殖。本研究利用前列腺腺癌转基因大鼠（TRAP）模型，聚焦于PGZ对前列腺癌发生的影响。PGZ处理以剂量依赖的方式显著降低了腹侧前列腺腺癌病变占总病变的百分比。PGZ处理也显著减少了腹侧前列腺每给定面积内腺癌的数量。PGZ还显著降低了腹侧前列腺中的Ki67标记指数。在PGZ处理的TRAP大鼠组中，检测到细胞周期蛋白D1表达降低，同时p38丝裂原活化蛋白激酶（MAPK）和核因子（NF）κB均失活。在人雄激素依赖性前列腺癌细胞系LNCaP中，PGZ也抑制细胞周期蛋白D1表达以及p38 MAPK和NFκB的激活。在LNCaP和人雄激素非依赖性前列腺癌细胞系PC3中，使用特异性抑制剂检测发现，培养细胞生长的抑制主要由NFκB途径调控。这些数据表明PGZ具有预防前列腺癌的潜力。
