Guo Yan-Tong, Leng Xi-Sheng, Li Tao, Zhao Jing-Ming, Lin Xi-Hou
Department of General Surgery, Beijing Jishuitan Hospital, the Forth Clinical Medical College of Peking University, Beijing 100035, China.
World J Gastroenterol. 2004 Dec 1;10(23):3419-23. doi: 10.3748/wjg.v10.i23.3419.
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 could induce cell differentiation and apoptosis, suggesting a potential application as chemopreventive agents against carcinogenesis. In the present study, 3 different kinds of PPARgamma ligands were subjected to the experiments to confirm their suppressive effects on liver carcinogenesis.
Three PPARgamma ligands, pioglitazone (Pio) (200 ppm), rosiglitazone (Rosi) (200 ppm), and troglitazone (Tro) (1,000 ppm) were investigated on the induction of the placental form of rat glutathione S-transferase (rGST P) positive foci, a precancerous lesion of the liver, and liver cancer formation using a diethylnitrosamine-induced liver cancer model in Wistar rats, and dose dependency of a PPARgamma ligand was also examined.
PPARgamma ligands reduced the formation of rGST P-positive foci by diethylnitrosamine and induction of liver cancers was also markedly suppressed by a continuous feeding of Pio at 200 ppm.
PPARgamma ligands are potential chemopreventive agents for liver 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价值。在本研究中，对3种不同的PPARγ配体进行实验以确认它们对肝癌发生的抑制作用。
使用Wistar大鼠二乙基亚硝胺诱导的肝癌模型，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）对大鼠谷胱甘肽S-转移酶胎盘形式（rGST P）阳性灶（一种肝脏癌前病变）的诱导作用以及肝癌形成的影响，同时还检测了PPARγ配体的剂量依赖性。
PPARγ配体减少了二乙基亚硝胺诱导的rGST P阳性灶的形成，并且持续给予200 ppm的Pio也显著抑制了肝癌的诱导。
PPARγ配体是肝癌发生的潜在化学预防剂。
