Quick Quincy A, Faison Milton O
Department of Biology, Southern University at New Orleans, New Orleans, LA 70126;
Exp Ther Med. 2012 Mar;3(3):487-492. doi: 10.3892/etm.2011.422. Epub 2011 Dec 19.
The unfolded protein endoplasmic reticulum stress response has emerged as a cellular physiological target to invoke tumor cell killing due to its homeostatic and cytoprotective functions. In this study, thapsigargin and tunicamycin, two endoplasmic reticulum stress inducers, were investigated for their efficacy on glioblastomas. We demonstrate that clinically relevant concentrations of thapsigargin and tunicamycin eliminate the glioblastoma cell reproductive capacity as a consequence of cell death. The mode of glioblastoma-induced cell death was determined to be via apoptosis as supported by increased C/EBP homologous protein (CHOP) levels and caspase 3 activity, two proteins with established roles in endoplasmic reticulum stress-induced cell death. In conclusion, this study provides evidence that glioblastomas are responsive to endoplasmic reticulum stress induction as a cellular program to eradicate this tumor via programmed cell death.
未折叠蛋白内质网应激反应因其稳态和细胞保护功能，已成为引发肿瘤细胞杀伤的细胞生理靶点。在本研究中，对两种内质网应激诱导剂毒胡萝卜素和衣霉素在胶质母细胞瘤上的疗效进行了研究。我们证明，临床相关浓度的毒胡萝卜素和衣霉素可导致胶质母细胞瘤细胞死亡，从而消除其繁殖能力。胶质母细胞瘤诱导的细胞死亡模式被确定为通过凋亡，这一结论得到了C/EBP同源蛋白（CHOP）水平升高和半胱天冬酶3活性增强的支持，这两种蛋白在内质网应激诱导的细胞死亡中发挥着既定作用。总之，本研究提供了证据表明，胶质母细胞瘤对内质网应激诱导有反应，这是一种通过程序性细胞死亡根除该肿瘤的细胞程序。
