期刊
JOURNAL OF NEURO-ONCOLOGY
卷 108, 期 3, 页码 385-393出版社
SPRINGER
DOI: 10.1007/s11060-012-0841-4
关键词
Soluble epoxide hydrolase; Inhibitor; Nuclear factor-kappa B; Glioma; Chemotherapy
资金
- Jiangsu Province Science Fund [BK2007257]
Although sEH inhibitors are well studied in inflammatory and cardiovascular diseases, their effects on gliomas are unclear. In this study, we investigated the effects of t-AUCB, a more potent and selective sEH inhibitor, on U251 and U87 human glioblastoma cell lines and the HepG2 human hepatocellular carcinoma cell line. Our results showed that t-AUCB efficiently inhibited sEH activities in all three cell lines (the inhibition rate was more than 80% in each) and suppressed U251 and U87 cell growth in a dose-dependent manner, but exhibited no cell growth inhibition on HepG2. We detected high levels of phosphorylated NF-kappa B-p65 (Ser536) in t-AUCB-treated U251 and U87 cells, and then found that the NF-kappa B inhibitor PDTC can completely abolish t-AUCB-induced growth inhibition. This indicated that t-AUCB suppresses U251 and U87 cell growth by activating NF-kappa B-p65. Moreover, we found that t-AUCB induces cell-cycle G0/G1 phase arrest by regulating Cyclin D1 mRNA and protein levels and CDC2 (Thr161) phosphorylation level. We propose to further test this promising reagent for its anti-glioma activity in clinical relevant orthotopic brain glioma models.
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