Zhang Qiu-Sheng, Zhang Meng, Huang Xian-Jian, Liu Xiao-Jia, Li Wei-Ping
Department of Neurosurgery, Shenzhen Clinical College Affiliated to Anhui Medical University, Shenzhen, Guandong 518000, P.R. China.
Department of Neurosurgery, Shenzhen 2nd People's Hospital, Shenzhen, Guangdong 508035, P.R. China.
Exp Ther Med. 2017 Jul;14(1):344-348. doi: 10.3892/etm.2017.4487. Epub 2017 May 22.
The purpose of this study was to further evaluate the role of myxoma virus (MYXV) as an oncolytic agent against experimental human gliomas , and analyze the effect of MYXV on malignant glioma cells at different incubation periods and infected at different multiplicities of infection. Neuroglioma cell lines U251 and A172 were cultured with various infective doses of myxoma virus at different time points (0-3 days) and cellular survival rates were evaluated using an MTT assay. Cell viability and cell death rates were assessed using Annexin V/propidium iodide and applying flow cytometry. Furthermore, the expression levels of phosphorylated AKT (p-AKT) in malignant gliomas were detected by western blot analysis to investigate the possible cell signaling targets in the pathway. MYXV exhibited a dose and time-dependent cytotoxic effect on neuroglioma cells, and there was increased expression of p-AKT in malignant gliomas. The present study confirms that MYXV induces oncolysis of malignant gliomas through regulating the activation of AKT. As such, MYXV is a potential therapeutic agent against human malignant gliomas.
本研究的目的是进一步评估黏液瘤病毒(MYXV)作为溶瘤剂对实验性人类胶质瘤的作用,并分析MYXV在不同孵育期以不同感染复数感染时对恶性胶质瘤细胞的影响。在不同时间点(0 - 3天)用不同感染剂量的黏液瘤病毒培养神经胶质瘤细胞系U251和A172,并使用MTT法评估细胞存活率。使用膜联蛋白V/碘化丙啶并应用流式细胞术评估细胞活力和细胞死亡率。此外,通过蛋白质印迹分析检测恶性胶质瘤中磷酸化AKT(p - AKT)的表达水平,以研究该途径中可能的细胞信号靶点。MYXV对神经胶质瘤细胞表现出剂量和时间依赖性的细胞毒性作用,并且恶性胶质瘤中p - AKT的表达增加。本研究证实MYXV通过调节AKT的激活诱导恶性胶质瘤的溶瘤作用。因此,MYXV是一种针对人类恶性胶质瘤的潜在治疗剂。