Ligands for peroxisome proliferator-activated receptor gamma have potent antitumor effect against human renal cell carcinoma

To examine whether peroxisome proliferator-activated receptor gamma (PPARγ) is expressed in human renal cell carcinoma (RCC) cells, and whether activation of PPARγ by its ligands can have multiple antitumor effects on human RCC cells in vitro. We examined the expression of PPARγ in four human RCC cell lines by reverse transcriptase-polymerase chain reaction and immunocytochemical staining. The effects of two PPARγ ligands, pioglitazone and 15-deoxy-Δ 12,14-prostaglandin J 2, on cell proliferation were investigated by 3-[4,5-dimethylthiazol-2-thiazoly]-2,5-diphenyltetrazolium bromide assay. The induction of apoptosis by the ligands was examined using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling method and Annexin V assay. Furthermore, we investigated whether these ligands suppressed the production of angiogenic factors, vascular endothelial growth factor and basic fibroblast growth factor, by enzyme-linked immunosorbent assay. PPARγ and retinoid X receptor, which forms a heterodimer with PPARγ, were expressed in all RCC cell lines. In addition, immunocytochemical studies showed expression of PPARγ protein in the RCC cells. PPARγ ligands inhibited the cell growth in all cells in a dose-dependent manner. These ligands also induced apoptosis. Furthermore, secretion of both vascular endothelial growth factor and basic fibroblast growth factor was inhibited by these ligands in a dose-dependent and time-dependent manner. Ligands for PPARγ have multiple antitumor effects in human RCC cells in vitro. Activation of the PPARγ pathway may be a new strategy for treatment of patients with RCC.