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过氧化物酶体增殖物激活受体γ配体对泌尿系统癌细胞的作用。

The effect of peroxisome proliferator-activated receptor-gamma ligand on urological cancer cells.

作者信息

Yoshimura Rikio, Matsuyama Masahide, Hase Taro, Tsuchida Kenji, Kuratsukuri Katsuyuki, Kawahito Yutaka, Sano Hajime, Segawa Yoshihiro, Nakatani Tatsuya

机构信息

Department of Urology, Osaka City University Graduate School of Medicine, University Hospital, 1-4-3 Asahi-machi, Abenoku, Osaka 545-8585, Japan.

出版信息

Int J Mol Med. 2003 Dec;12(6):861-5.

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.

摘要

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。

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