The Role of PPAR gamma in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. This cancer develops mainly in cirrhotic patients. The cirrhotic liver is considered to be a preneoplastic organ, suggesting the rationale for cancer prevention. PPAR gamma is a nuclear transcription factor whose activation leads to interaction in the metabolism of lipids, insulin sensitization of peripheral cells, anti-inflammatory action. It can also induce differentiation and inhibits proliferation of cancer cells. Until now, data using PPAR gamma ligands in HCC have demonstrated mainly in in vitro models that its activation could be due to an antiproliferative effect. PPAR gamma ligand administration has also been associated with a diminution of liver fibrosis in animal models, and potentially also on tumoral cell death. Soma data show that the favorable effect of natural and synthetized PPAR gamma agonists could also be independent of PPAR gamma activation. Furthermore, in some situations, PPAR gamma antagonists have also an anticancer effect. Therefore, we can conclude that the link between activation of the PPAR gamma pathway and an anticancer activity is suggested but until now not firmly established in HCC. Copyright (C) 2008 I. Borbath and Y. Horsmans.