BET inhibitor I-BET151 sensitizes GBM cells to temozolomide via PUMA induction
2019
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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