Abstract
A significant roadblock in treatment of GBM multiforme (GBM) is resistance to temozolomide (TMZ). In this study, we investigated whether I-BET151, a specific BET inhibitor, could sensitize GBM cells to TMZ. Our findings showed that the action of I-BET151 could augment the effect of TMZ on cancer cells U251 and U87 cells. In U251 cells, administration of I-BET151 increased the TMZ-induced apoptosis GBM cells. I-BET151 remarkably enhanced the activities of caspase-3. In addition, I-BET151 promoted TMZ-induced migration and invasion in GBM cells. Moreover, I-BET151 increased the amount of reactive oxygen species as well as superoxide anions with a decrease of activity of SOD and the anti-oxidative properties of GBM cells. I-BET151 also induced increased PUMA expression, which is required for the functions of I-BET151 and regulates the synergistic cytotoxic effects of i-BET151 and TMZ in GBM cells. I-BET151 with TMZ also showed synergistic cytotoxic effects in vivo. These point out to an approach to tackle GBM using TMZ along with BET inhibitors.
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Change history
01 February 2019
All animal experiments were approved by the Animal Care and Use Committee (ACUC), Louisiana State University Health Science Center and not The People's Hospital of Liaoning Province as indicated in the original version of the Article. The PDF and HTML versions of the Article have been modified accordingly.
20 September 2022
This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1038/s41417-022-00536-4
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Yao, Z., Yang, S., Zhao, H. et al. RETRACTED ARTICLE: BET inhibitor I-BET151 sensitizes GBM cells to temozolomide via PUMA induction. Cancer Gene Ther 27, 226–234 (2020). https://doi.org/10.1038/s41417-018-0068-4
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DOI: https://doi.org/10.1038/s41417-018-0068-4