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The effect of peroxisome proliferator-activated receptor-gamma ligand on urological cancer cells
Authors:Yoshimura Rikio  Matsuyama Masahide  Hase Taro  Tsuchida Kenji  Kuratsukuri Katsuyuki  Kawahito Yutaka  Sano Hajime  Segawa Yoshihiro  Nakatani Tatsuya
Affiliation:Department of Urology, Osaka City University Graduate School of Medicine, University Hospital, 1-4-3 Asahi-machi, Abenoku, Osaka 545-8585, Japan. jasmin@med.osaka-cu.ac.jp
Abstract:Peroxisome proliferator activator-receptor (PPAR)-gamma ligand induces growth arrest of cancer cells through apoptosis. In this study, we examined the effects of PPAR-gamma inhibitors on cell proliferation in renal cell carcinoma (RCC), bladder tumor (BT), and prostatic carcinoma (PC) cell lines. We investigated the inhibitory effect of PPAR-gamma ligands, troglitazone and 15-deoxy-Delta12,14-prostaglandin J2 (15dPGJ2) on RCC, BT and PC-derived cell lines using MTT assay and Hoechst staining. PPAR-gamma ligands (troglitazone and 15dPGJ2) induced the reduction of cell viability with the half-maximal concentration of growth inhibition of RCC, BT, and PC cell lines. Furthermore, counting cells at days 1, 2 and 3, clearly showed marked inhibition of cell proliferation using troglitazone and 15dPGJ2. All PPAR-gamma inhibitors stopped the growth of all RCC, BT and PC cells. Cells treated with PPAR-gamma inhibitors showed chromatin condensation, cellular shrinkage, small membrane-bound bodies (apoptotic bodies), and cytoplasmic condensation. These cellular changes were typically redundant characteristics of apoptosis. PPAR-gamma ligands may mediate potent antiproliferative effects against RCC, BT and PC cells through differentiation. Thus, PPAR-gamma may become a new target in treatment of urological tumors.
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