Osawa Emi, Nakajima Atsushi, Wada Koichiro, Ishimine Satoko, Fujisawa Nobutaka, Kawamori Toshihiko, Matsuhashi Nobuyuki, Kadowaki Takashi, Ochiai Masako, Sekihara Hisahiko, Nakagama Hitoshi
The Third Department of Internal Medicine, Yokohama City University School of Medicine, Japan.
Gastroenterology. 2003 Feb;124(2):361-7. doi: 10.1053/gast.2003.50067.
BACKGROUND & AIMS: Peroxisome proliferator-activated receptor gamma (PPARgamma) is known to regulate growth arrest and terminal differentiation of adipocytes and is used clinically as a new class of antidiabetic drugs. Recently, several studies have reported that treatment of cancer cells with PPARgamma ligands induces cell differentiation and apoptosis, suggesting a potential application as chemopreventive agents against carcinogenesis. However, contradictory results have been reported with regards to the biologic role of PPARgamma in carcinogenesis. Tanaka et al.(24) have recently reported the suppressive effect of a PPARgamma ligand, troglitazone (Tro), on the formation of aberrant crypt foci (ACF) in rats. In the present study, 3 different kinds of PPARgamma ligands were subjected to the experiments to confirm their suppressive effects on colon carcinogenesis.
Three PPARgamma ligands, pioglitazone (Pio) (200 ppm), rosiglitazone (Rosi) (200 ppm), and Tro (1000 ppm) were investigated on the induction of ACF, a putative precancerous lesion of the colon, and colon tumor formation using an azoxymethane (AOM)-induced colon cancer model in BALB/c mice, and dose dependency of a PPARgamma ligand was also examined.
PPARgamma ligands reduced the ACF formation by AOM (10 mg/kg body weight) and induction of colon tumors were also markedly suppressed by a continuous feeding of Pio at 200 ppm.
Our findings indicate that PPARgamma ligands are indeed potential chemopreventive agents for colon carcinogenesis.
已知过氧化物酶体增殖物激活受体γ（PPARγ）可调节脂肪细胞的生长停滞和终末分化，并且在临床上用作一类新型抗糖尿病药物。最近，多项研究报道用PPARγ配体处理癌细胞可诱导细胞分化和凋亡，提示其作为化学预防剂预防癌变的潜在应用。然而，关于PPARγ在癌变中的生物学作用已报道了相互矛盾的结果。Tanaka等人（24）最近报道了一种PPARγ配体曲格列酮（Tro）对大鼠异常隐窝灶（ACF）形成的抑制作用。在本研究中，对3种不同的PPARγ配体进行实验以证实它们对结肠癌发生的抑制作用。
使用偶氮甲烷（AOM）诱导的BALB/c小鼠结肠癌模型，研究了3种PPARγ配体，即吡格列酮（Pio）（200 ppm）、罗格列酮（Rosi）（200 ppm）和曲格列酮（Tro）（1000 ppm）对ACF（一种假定的结肠癌前病变）诱导和结肠肿瘤形成的影响，并且还检测了PPARγ配体的剂量依赖性。
PPARγ配体减少了AOM（10 mg/kg体重）诱导的ACF形成，并且持续喂食200 ppm的Pio也显著抑制了结肠肿瘤的诱导。
我们的研究结果表明，PPARγ配体确实是结肠癌发生的潜在化学预防剂。
