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

Du,Jun; Wang,Ruijie; Yin,Litian; Fu,Yuejun; Cai,Yuqing; Zhang,Zhiyun; Liang,Aihua

doi:10.3892/ol.2017.7483

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

Authors:
- Jun Du
- Ruijie Wang
- Litian Yin
- Yuejun Fu
- Yuqing Cai
- Zhiyun Zhang
- Aihua Liang
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Affiliations: Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan, Shanxi 030006, P.R. China, Department of Physiology, Key Laboratory of Cellular Physiology Co‑Constructed by Province and Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030006, P.R. China
Published online on: November 24, 2017 https://doi.org/10.3892/ol.2017.7483
Pages: 1537-1544
Copyright: © Du et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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 (BmK CT) markedly inhibited cell proliferation and induced apoptosis in U251 cells when combined with TMZ. In combination with TMZ, BmK 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, BmK 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 BmK CT enhanced the sensitivity of TMZ‑induced U251 cell apoptosis through the downregulation of phosphorylated AKT levels, suggesting that BmK CT and TMZ combination therapy may be a novel approach for glioma therapy.

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