Yoshimura Rikio, Matsuyama Masahide, Hase Taro, Tsuchida Kenji, Kuratsukuri Katsuyuki, Kawahito Yutaka, Sano Hajime, Segawa Yoshihiro, Nakatani Tatsuya
Department of Urology, Osaka City University Graduate School of Medicine, University Hospital, 1-4-3 Asahi-machi, Abenoku, Osaka 545-8585, Japan.
Int J Mol Med. 2003 Dec;12(6):861-5.
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.
过氧化物酶体增殖物激活受体(PPAR)-γ配体通过诱导凋亡使癌细胞生长停滞。在本研究中,我们检测了PPAR-γ抑制剂对肾细胞癌(RCC)、膀胱肿瘤(BT)和前列腺癌细胞系细胞增殖的影响。我们使用MTT法和Hoechst染色研究了PPAR-γ配体曲格列酮和15-脱氧-Δ12,14-前列腺素J2(15dPGJ2)对RCC、BT和PC来源的细胞系的抑制作用。PPAR-γ配体(曲格列酮和15dPGJ2)可诱导RCC、BT和PC细胞系的细胞活力降低,半数最大生长抑制浓度出现。此外,在第1、2和3天对细胞进行计数,清楚地显示使用曲格列酮和15dPGJ2可显著抑制细胞增殖。所有PPAR-γ抑制剂均能阻止所有RCC、BT和PC细胞的生长。用PPAR-γ抑制剂处理的细胞表现出染色质浓缩、细胞皱缩、小的膜结合体(凋亡小体)和细胞质浓缩。这些细胞变化是凋亡的典型特征。PPAR-γ配体可能通过分化介导对RCC、BT和PC细胞的有效抗增殖作用。因此,PPAR-γ可能成为治疗泌尿系统肿瘤的新靶点。