Peroxisome proliferator-activated receptor gamma ligands suppress liver carcinogenesis induced by diethylnitrosamine in rats.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
PPARgamma ligands are potential chemopreventive agents for liver carcinogenesis.
Guo
Yan-Tong
YT
Department of General Surgery, Beijing Jishuitan Hospital, the Forth Clinical Medical College of Peking University, Beijing 100035, China. guoyantong2002@sohu.com
Leng
Xi-Sheng
XS
Li
Tao
T
Zhao
Jing-Ming
JM
Lin
Xi-Hou
XH
D000477:Alkylating Agents; D000818:Animals; D016588:Anticarcinogenic Agents / Q000378:metabolism / Q000494:pharmacology*; D002839:Chromans / Q000378:metabolism / Q000494:pharmacology; D004052:Diethylnitrosamine; D015870:Gene Expression; D005982:Glutathione Transferase / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000378:metabolism / Q000494:pharmacology*; D007150:Immunohistochemistry; D008024:Ligands; D008113:Liver Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D000077205:Pioglitazone; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000378:metabolism / Q000494:pharmacology*; D000077288:Troglitazone
D000477:Alkylating Agents; D016588:Anticarcinogenic Agents; D002839:Chromans; D007004:Hypoglycemic Agents; D008024:Ligands; D047495:PPAR gamma; D012333:RNA, Messenger; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D004052:Diethylnitrosamine; D005982:Glutathione Transferase; D000077288:Troglitazone; D000077205:Pioglitazone