The apoptosis-resistance in t-AUCB-treated glioblastoma cells depends on activation of Hsp27
The apoptosis-resistance in t-AUCB-treated glioblastoma cells depends on activation of Hsp27
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DOI：
10.1007/s11060-012-0963-8
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发表时间：
2012-11-01
影响因子：
3.9
通讯作者：
Lan, Qing
中科院分区：
文献类型：
--
作者：
Li, Junyang;Hu, Weixing;Lan, Qing
我们先前报道了sEH抑制剂t-AUCB抑制人胶质母细胞瘤U251和U87细胞的生长，并诱导细胞周期G0/G1期停滞。在本研究中，我们发现200 mU Mt-AUCB作用96h也不能诱导U251和U87细胞发生凋亡。我们还发现，200 mU的mt-AUCB显著提高了p38 MAPK、MAPKAPK2和Hsp27的活性。用p38MAPK抑制剂SB203580和Hsp27磷酸化抑制剂KRIBB3研究其抗凋亡机制。结果表明，用SB203580或KRIBB3阻断Hsp27的激活后，200 mU Mt-AUCB可显著诱导U251和U87细胞的凋亡，并增加caspase-3活性。我们的研究结果表明，t-AUCB在阻断其自身诱导的Hsp27激活后可诱导细胞凋亡，并且Hsp27的激活可能导致GBM细胞产生化疗耐药。联合应用t-AUCB和Hsp27磷酸化抑制物可能是治疗胶质母细胞瘤的一种潜在策略。
We previously reported that sEH inhibitor t-AUCB suppresses the growth of human glioblastoma U251 and U87 cell lines and induces cell-cycle G0/G1 phase arrest. In present study, we found even 96 h-treatment of 200 mu M t-AUCB can not induce apoptosis in U251 and U87 cells. We also revealed that 200 mu Mt-AUCB significantly elevates the activation of p38 MAPK, MAPKAPK2 and Hsp27. The p38 MAPK inhibitor SB203580 and the inhibitor of Hsp27 phosphorylation, KRIBB3, were used to investigate the mechanism of the apoptosis-resistance. The results showed that, after blocking the activation of Hsp27 by SB203580 or KRIBB3, 200 mu M t-AUCB significantly induces apoptosis and increases caspase-3 activities in U251 and U87 cells. Our data demonstrated that t-AUCB induces cell apoptosis after blocking itself-induced activation of Hsp27, and that the activation of Hsp27 may confer chemoresistance in GBM cells. The combination of t-AUCBand the inhibitor of Hsp27 phosphorylation may be a potential strategy for treatment of glioblastoma.