Inhibition of peroxisome proliferator‐activated receptor gamma activity in esophageal carcinoma cells results in a drastic decrease of invasive properties

Esophageal cancer is difficult to treat because of its rapid progression, and more effective therapeutic approaches are needed. The PPARγ is a nuclear receptor superfamily member that is expressed in many cancers. PPARγ expression is a feature of esophageal cancer cell lines, and in the present investigation, the PPARγ antagonists T0070907 and GW9662 could induce loss of invasion but could not induce growth reduction or apoptosis at low concentrations (<10 mM). A high concentration of antagonists (50 µM) inhibited cell growth and induced apoptosis, but these effects did not explain our result at the low concentration. Morphological change, decreased expression of the cell signaling pathway and inhibition of cancer cell invasion were observed in the low concentration. This suggested that PPARγ antagonists inhibited esophageal cancer cell invasion as well as cell adherence, most likely due to alteration in the FAK–MAPK pathway, and this was independent of apoptosis. These results suggested that PPARγ plays an important role in cancer cell invasion and that it might be a novel target for therapy of esophageal cancer. ( Cancer Sci 2006; 97: 854–860)