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The apoptosis-resistance in t-AUCB-treated glioblastoma cells depends on activation of Hsp27

  • Laboratory Investigation
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Abstract

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 μM t-AUCB can not induce apoptosis in U251 and U87 cells. We also revealed that 200 μM t-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 μM 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-AUCB and the inhibitor of Hsp27 phosphorylation may be a potential strategy for treatment of glioblastoma.

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Acknowledgments

We thank Professor Bruce D. Hammock for providing the sEH inhibitor t-AUCB. This study was supported by research fund from Chinese Ministry of Health (No. WKJ20052031).

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Authors and Affiliations

  1. Department of Neurosurgery, Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, Jiangsu, China

    Junyang Li & Qing Lan

  2. Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China

    Weixing Hu

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  1. Junyang Li
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Correspondence to Qing Lan.

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Li, J., Hu, W. & Lan, Q. The apoptosis-resistance in t-AUCB-treated glioblastoma cells depends on activation of Hsp27. J Neurooncol 110, 187–194 (2012). https://doi.org/10.1007/s11060-012-0963-8

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