Zhicheng Yao, Shida Yang, Hongyou Zhao, Huike Yang, Xin Jiang
Cancer gene therapy 2020 AprA 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.
Zhicheng Yao, Shida Yang, Hongyou Zhao, Huike Yang, Xin Jiang. BET inhibitor I-BET151 sensitizes GBM cells to temozolomide via PUMA induction. Cancer gene therapy. 2020 Apr;27(3-4):226-234
PMID: 30518782
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