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Temozolomide and AZD7762 Induce Synergistic Cytotoxicity Effects on Human Glioma Cells
Yun Chen1,2, Bor-Jiun Tseng1, Ya-Hui Tsai1,2
1Department of Surgery, Far Eastern Memorial Hospital, New Taipei, Taiwan, R.O.C.
Background/Aim:
This study investigated the effects of temozolomide (TMZ) and/or checkpoint kinase inhibitor AZD7762 in human glioma cells.
Materials And Methods:
Glioma cells were treated with TMZ and/or AZD7762 for 24 or 48 h, then the cellular survival was studied and the expression of various proteins was investigated.
Results:
Both TMZ and AZD7762 induced concentration- and time-dependent cytotoxic effects, and combined TMZ and AZD7762 (TMZ+AZD) caused synergistic cytotoxic effects in glioma cells (p<0.05). AZD7762 suppressed the O6-methylguanine-DNA-methyltransferase (MGMT) expression. TMZ+AZD increased the expression of phospho-p53 (p-p53), p-p38 mitogen-activated protein kinase, and phosphatase and tensin homolog; and decreased the expression of p-extracellular signal-regulated kinase 1/2 and p-signal transducer and activator of transcription 3 in glioma cells.
Conclusion:
TMZ and AZD7762 combined induced synergistic cytotoxic effects on human glioma cells and such effects may be related to the AZD7762-induced suppression of MGMT expression and the modulation of multiple signaling pathways.
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