Pioglitazone inhibits growth of carcinoid cells and promotes TRAIL-induced apoptosis by induction of p21waf1/cip1

被引:60
|
作者
Göke, R
Göke, A
Göke, B
El-Deiry, WS
Chen, YH
机构
[1] Univ Penn, Sch Med, Dept Mol & Cellular Engn, Philadelphia, PA 19104 USA
[2] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA
[3] Univ Munich, Klinikum Grosshadern, Dept Internal Med 2, D-8000 Munich, Germany
关键词
pioglitazone; carcinoid; TRAIL; apoptosis; p21(waf1/cip1);
D O I
10.1159/000048843
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background/Aims: We investigated the effect of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist pioglitazone on growth and TRAIL-induced apoptosis in carcinoid cells. Methods: Carcinoid cells were incubated without and with pioglitazone. Effects on growth were examined by cell count and cell cycle analysis. p21(waf1/cip1) expression was determined by Western blotting. Cytotoxicity assay was performed by FACS analysis. Results: Pioglitazone suppressed the growth and induced apoptosis of carcinoid cells. Additionally, pioglitazone significantly enhanced carcinoid cell death induced by tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL). The enhancement of TRAIL-induced apoptosis was associated with an upregulation of cyclin-dependent kinase inhibitor p21(waf1/cip1) in pioglitazone-treated carcinoid cells. Importantly, overexpression of p21(waf1/cip1) in carcinoid cells by adenoviral gene transfer of p21 sensitized them to TRAIL-induced apoptosis. Conclusions: These results suggest that pioglitazone inhibits cell growth and sensitizes cells to TRAIL-induced apoptosis by induction of p21(waf1/cip1). Therefore, pioglitazone can be an effective therapeutic adjuvant for the treatment of carcinoid tumors. Copyright (C) 2001 S. Karger AG, Basel.
引用
收藏
页码:75 / 80
页数:6
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