BET inhibitor I-BET151 sensitizes GBM cells to temozolomide via PUMA induction

Zhicheng Yao, Shida Yang, Hongyou Zhao, Huike Yang, Xin Jiang*

*此作品的通讯作者

科研成果: 期刊稿件文章同行评审

9 引用 (Scopus)

摘要

A significant roadblock in treatment of GBM multiforme (GBM) isresistance to temozolomide (TMZ). In this study, we investigated whether I-BET151, aspecific BET inhibitor, could sensitize GBM cells to TMZ. Our findings showed thatthe action of I-BET151 could augment the effect of TMZ on cancer cells U251 and U87cells. In U251 cells, administration of I-BET151 increased the TMZ-induced apoptosisGBM 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 superoxideanions with a decrease of activity of SOD and the anti-oxidative properties of GBMcells. I-BET151 also induced increased PUMA expression, which is required for thefunctions of I-BET151 and regulates the synergistic cytotoxic effects of i-BET151and TMZ in GBM cells. I-BET151 with TMZ also showed synergistic cytotoxic effects invivo. These point out to an approach to tackle GBM using TMZ along with BETinhibitors.

源语言英语
页(从-至)226-234
页数9
期刊Cancer Gene Therapy
27
3-4
DOI
出版状态已出版 - 1 4月 2020
已对外发布

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Yao, Z., Yang, S., Zhao, H., Yang, H., & Jiang, X. (2020). BET inhibitor I-BET151 sensitizes GBM cells to temozolomide via PUMA induction. Cancer Gene Therapy, 27(3-4), 226-234. https://doi.org/10.1038/s41417-018-0068-4