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 |
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页(从-至) | 226-234 |
页数 | 9 |
期刊 | Cancer Gene Therapy |
卷 | 27 |
期 | 3-4 |
DOI | |
出版状态 | 已出版 - 1 4月 2020 |
已对外发布 | 是 |