Temozolomide (TMZ) is used in the standard therapy regimen for patients with glioblastoma (GBM). However, some GBM patients do not respond to TMZ therapy. The combining therapeutic agents in GBM treatment are attracting considerable interest due to TMZ resistance. This study aims to identify the combinatorial effect of TMZ and AZD3463 on the viability of the T98G GBM cells. The cytotoxic effects of compounds were determined by using WST-8 assay. Flow cytometry was used to determine apoptosis and cell cycle profiles after treatments. Real-time PCR was used to identify mRNA expression of genes in the PI3K/AKT signaling pathway after treatments. IC₅₀ concentrations of TMZ and AZD3463 were found to be 1.54 mM and 529 nM after incubation for 48 h, respectively. The combination treatment showed a synergistic effect on reducing the viability of GBM cells. Each one of TMZ, AZD3463, and combination treatments induced apoptosis. Treatments, either alone or the combination of these agents, caused the cell cycle arrest in distinct phases. TMZ and AZD3463 treatments, either alone or in combination, downregulated mRNA expression of genes in the PI3K/AKT signaling pathway. The combination of TMZ with AZD3463 may increase the efficacy of single TMZ treatment in GBM cells due to decreased expression of genes in the PI3K/AKT signaling pathway that is responsible for drug resistance and intratumoral heterogeneity.

替莫唑胺（TMZ）用于胶质母细胞瘤（GBM）患者的标准治疗方案。但是，某些GBM患者对TMZ治疗无反应。由于TMZ抗性，GBM治疗中的组合治疗剂引起了极大的兴趣。这项研究旨在确定TMZ和AZD3463对T98G GBM细胞活力的组合作用。通过使用WST-8测定法测定化合物的细胞毒性作用。流式细胞仪用于确定治疗后的细胞凋亡和细胞周期概况。治疗后，实时PCR用于鉴定PI3K / AKT信号通路中基因的mRNA表达。IC ₅₀孵育48小时后，TMZ和AZD3463的浓度分别为1.54 mM和529 nM。联合治疗对降低GBM细胞的活力具有协同作用。TMZ，AZD3463和联合治疗中的每一种均诱导细胞凋亡。单独或组合使用这些治疗剂，可使细胞周期停滞在不同的阶段。单独或组合使用TMZ和AZD3463处理，均可下调PI3K / AKT信号通路中基因的mRNA表达。TMZ与AZD3463的组合可提高GBM细胞中单一TMZ治疗的功效，这是由于负责耐药性和肿瘤内异质性的PI3K / AKT信号通路中基因的表达减少。