Emerging role of the peroxisome proliferator-activated receptor-gamma in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the major leading cause of cancer death worldwide. Hepatitis B virus, hepatitis C virus, alcohol consumption, non-alcoholic fatty liver disease, and diabetes are the major risks for developing HCC. Until now, recurrence and metastasis are the major cause of death in HCC patients. Therefore, identification of new effective molecular targets is an urgent need for treatment of HCC. Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a ligand-activated nuclear receptor which could be activated by PPAR. agonists such as thiazolidinediones, and natural PPAR. ligand (such as 15-deoxy-Delta 12,14prostaglandin J(2), 15d-PGJ(2)). Increasing in vitro and in vivo evidence has demonstrated that PPAR. agonists exhibit an inhibitory role on tumor cell growth, migration, and invasion, suggesting that PPAR. activation may play an important role in the regulation of growth of HCC. It has been reported that PPAR gamma activation by thiazolidinediones or overexpression of PPAR gamma by virus-mediated gene transfer has shown growth inhibitory effects in hepatoma cells, but the expression level of PPAR gamma in HCC tissues still remains conflicting. Notably, a novel PPAR. agonist, honokiol, has recently been found to activate the PPAR gamma/RXR heterodimer, and has also exhibited significant anti-cancer effects in hepatoma cells. In the present review, we summarized studies on the role and the molecular regulation of PPAR gamma in HCC development in vitro and in vivo. PPAR gamma has the potential to be a therapeutic target for future treatment of HCC.