15-deoxy-Δ12,14-prostaglandin J2, a ligand for peroxisome proliferators-activated receptor-γ, induces apoptosis in human hepatoma cells
15-deoxy-Δ12,14-prostaglandin J2, a ligand for peroxisome proliferators-activated receptor-γ, induces apoptosis in human hepatoma cells
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DOI：
10.1111/j.1478-3231.2003.00877.x
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发表时间：
2003-12-01
影响因子：
6.7
通讯作者：
Ohura, K
中科院分区：
文献类型：
--
作者：
Date, M;Fukuchi, K;Ohura, K
背景/目标：15-脱氧-δ（12，14）-前列腺素J（2）（15-d-PGJ（2））在几种癌细胞系中诱导凋亡，并且是过氧化物酶体增殖物激活受体-γ（PPAR-gamma）的有效激活剂。在本研究中，我们研究了15-d-PGJ（2）对人肝癌细胞的作用。方法：采用HuH-7和HepG 2细胞系进行实验。采用逆转录聚合酶链反应（RT-PCR）检测PPAR-gamma mRNA的表达。通过改良的MTT法测定细胞活力。两种方法用于测定肝癌细胞中的凋亡：TUNEL测定，以及通过ELISA检测片段化的单核小体和寡核小体。结果：HuH-7和HepG 2细胞中均检测到PPAR-gamma mRNA和蛋白的表达。用15-d-PGJ（2）处理以时间和剂量依赖性方式降低细胞活力。15-d-PGJ（2）可诱导细胞凋亡，并呈时间依赖性。细胞暴露于15-d-PGJ（2）诱导caspase-3和-9活化。此外，与泛半胱天冬酶抑制剂Z-VAD-FMK或半胱天冬酶-3抑制剂Z-DEVD-FMK共同处理可阻断已用15-d-PGJ处理的人肝癌细胞的凋亡（2）。结论：我们的研究表明，PPAR-gamma在人肝癌细胞系中表达，15-d-PGJ（2）通过激活半胱天冬酶诱导细胞凋亡抑制这些细胞的生长。
Background/Aims: 15-deoxy-Delta(12,14)-prostaglandin J(2) (15-d-PGJ(2)) induces apoptosis in several carcinoma cell lines and is a potent activator of peroxisome proliferators-activated receptor-gamma (PPAR-gamma). In the present study, we examined the effect of 15-d-PGJ(2) on human hepatoma cells. Methods: HuH-7 and HepG2 cell lines were used in all the experiments. The mRNA expression of PPAR-gamma was studied by reverse transcriptase-polymerase chain reaction. The cell viability was determined by a modified MTT assay. Two methods were used for the determination of apoptosis in hepatoma cells: the TUNEL assay, and detection of fragmented mono- and oligo-nucleosomes by ELISA. Results: The expression of PPAR-gamma mRNA and protein was detected in HuH-7 and HepG2. Treatment with 15-d-PGJ(2) decreased cell viability in a time- and dose-dependent manner. 15-d-PGJ(2) induced apoptosis and this effect was time-dependent. Exposure of cells to 15-d-PGJ(2) induced caspase-3 and -9 activation. Furthermore, co-treatment with the pan-caspase inhibitor Z-VAD-FMK or the caspase-3 inhibitor Z-DEVD-FMK blocked apoptosis of human hepatoma cells that had been treated with 15-d-PGJ(2). Conclusions: Our study demonstrates that PPAR-gamma is expressed in human hepatoma cell lines and that treatment with 15-d-PGJ(2) inhibits the growth of these cells by inducing apoptosis through caspase activation.