Establish the chemopreventive strategy using PPAR gamma ligands for colorectal cancer

点击翻译按钮获取中文摘要

Activating synthetic ligands for PPARY, such as pioglitazone and rosiglitazone, are commonly used to treat patients with diabetes mellitus (DM) in order to improve insulin resistance. Several reports have clearly demonstrated that PPARY ligands, could inhibit colorectal cancer cell growth and induce apoptosis. On the other hands, the insulin resistance or hyper insulinemia are thought to be the one of the major risk factors of colorectal cancer (CRC). If hyper insulinemia, alone or in combination with other features of the insulin resistance syndrome, is associated with increased risk of CRC, activation of PPARY may play a benefited role in colon carcinogenesis. The results of clinical trials for CRC with PPARY ligands have shown modest This implies that aiming at PPARY as a specific anti-tumor target is not likely to be successful, because PPARY ligands are not an active agent for the treatment of advanced or metastatic CRC. Recently, we have demonstrated the substantial suppressive effects of PPARY ligands on colon carcinogenesis in mouse model in the early stage of carcinogenesis, suggesting a potential application as the chemopreventive agents against carcinogenesis. Furthermore, number of aberrant crypt foci, pre cancerous lesion of colorectal, was significantly decreased by PPARY ligand treatment in human study. PPARY ligands are used with safety benefit and may be a clinical application as anti-cancer drug in early stage of CRC. These results suggest that PPARY ligand is a promising candidate as a chemopreventive agent for CRC.