Du Jun, Wang Ruijie, Yin Litian, Fu Yuejun, Cai Yuqing, Zhang Zhiyun, Liang Aihua
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.
Oncol Lett. 2018 Feb;15(2):1537-1544. doi: 10.3892/ol.2017.7483. Epub 2017 Nov 24.
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 Kirsch (K CT) markedly inhibited cell proliferation and induced apoptosis in U251 cells when combined with TMZ. In combination with TMZ, K CT exhibited a significant and synergistic anti-tumor effect by inhibiting protein kinase B (AKT) independently and triggering the apoptosis signaling cascade . Furthermore, 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 K CT enhanced the sensitivity of TMZ-induced U251 cell apoptosis through the downregulation of phosphorylated AKT levels, suggesting that K CT and TMZ combination therapy may be a novel approach for glioma therapy.
替莫唑胺（TMZ）是一种已被证明在与同步放疗联合使用时可改善多形性胶质母细胞瘤（GBM）患者生存时间的药物。然而，化疗耐药是GBM治疗中的主要障碍之一。在本研究中，采用MTT法和流式细胞术证明，蝎子基尔氏蝎毒液中的类氯毒素（K CT）与TMZ联合使用时，可显著抑制U251细胞的增殖并诱导其凋亡。与TMZ联合使用时，K CT通过独立抑制蛋白激酶B（AKT）并触发凋亡信号级联反应，表现出显著的协同抗肿瘤作用。此外，K CT在转录水平上增加了磷酸酶和张力蛋白同源物的表达，这是AKT信号通路的关键负调节因子。本研究结果表明，K CT通过下调磷酸化AKT水平增强了TMZ诱导的U251细胞凋亡的敏感性，提示K CT与TMZ联合治疗可能是一种治疗胶质瘤的新方法。
