B m K CT enhances the sensitivity of temozolomide-induced apoptosis of malignant glioma U251 cells in vitro through blocking the AKT signaling pathway.

Temozolomide (TMZ) is a drug that has been demonstrated to improve the survival time of patients with glioblastoma multiforme (GBM) when administered with concomitant radiotherapy. However, chemoresistance is one of the major obstacles in the treatment of GBM. In the present study, an MTT assay and flow cytometry were used to demonstrate that chlorotoxin-like toxin in the venom of the scorpion Buthus martensii Kirsch ( Bm K CT) markedly inhibited cell proliferation and induced apoptosis in U251 cells when combined with TMZ. In combination with TMZ, Bm K CT exhibited a significant and synergistic anti-tumor effect by inhibiting protein kinase B (AKT) independently and triggering the apoptosis signaling cascade in vitro . Furthermore, Bm K CT increased the expression of phosphatase and tensin homolog at the transcriptional level, which is a key negative regulator of the AKT signaling pathway. The results of the present study demonstrated that Bm K CT enhanced the sensitivity of TMZ-induced U251 cell apoptosis through the downregulation of phosphorylated AKT levels, suggesting that Bm K CT and TMZ combination therapy may be a novel approach for glioma therapy.