Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
NMR Biomed. 2010 Jun;23(5):473-9. doi: 10.1002/nbm.1484.
The effects of the selective peroxisome proliferator activated receptor-gamma (PPAR-gamma) inhibitor GW9662 on phenylbutyrate (PB)-induced NMR-detectable lipid metabolites was investigated on DU145 prostate cancer cells. DU145 cells were perfused with 10 mM PB in the presence or absence of 1 microM of GW9662 and the results monitored by (31)P and diffusion-weighted (1)H NMR spectroscopy. GW9662 completely reversed PB-induced NMR-visible lipid and total choline accumulation in (1)H spectra and glycerophosphocholine and beta-NTP in (31)P spectra. In addition, pre-incubation with GW9662 significantly reduced PB-induced caspase-3 activation, reversed the G(1) block as measured by flow cytometry, and otherwise had little effect on cell survival as measured by MTT assay. These results suggest that the NMR visible lipid accumulation and apoptosis induced by PB treatment occurs through a mechanism that is mediated by PPAR-gamma.
研究了过氧化物酶体增殖物激活受体-γ（PPAR-γ）抑制剂 GW9662 对苯丁酸钠（PB）诱导的 NMR 可检测脂质代谢物的影响，该研究在 DU145 前列腺癌细胞上进行。DU145 细胞在存在或不存在 1 μM GW9662 的情况下用 10 mM PB 灌注，并通过（31）P 和扩散加权（1）H NMR 光谱监测结果。GW9662 完全逆转了 PB 诱导的（1）H 谱中 NMR 可见脂质和总胆碱的积累，以及（31）P 谱中甘油磷酸胆碱和β-NTP。此外，GW9662 的预孵育显著降低了 PB 诱导的 caspase-3 激活，通过流式细胞术逆转了 G1 阻断，并且在用 MTT 测定法测量细胞存活率方面几乎没有其他影响。这些结果表明，PB 处理诱导的 NMR 可见脂质积累和细胞凋亡是通过 PPAR-γ 介导的机制发生的。
