Deng Xin, Zhao Wen, Song Laijun, Ying Wei, Guo Xinbin
Department of Neuro-Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
Oncol Lett. 2018 Apr;15(4):5004-5012. doi: 10.3892/ol.2018.7977. Epub 2018 Feb 7.
Glioma is one of the most common aggressive neuroepithelial malignant tumors in the central nervous system. It has a high recurrence rate and poor prognosis, primarily due to the fact that novel therapeutic agents cannot penetrate the blood-brain barrier (BBB). Endothelial progenitor cells (EPCs) have been reported to move across the BBB and access the tumor site. However, whether EPCs expressing the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induce glioma cell apoptosis requires further investigation. In the present study, EPCs were transfected and stably expressed with TRAIL through lentiviral infection. The pro-apoptotic effect of these TRAIL-expressing EPCs on the SHG44 glioma cell line was investigated. The migration ability of TRAIL-expressing EPCs toward SHG44 cells through the Transwell culture system was investigated via a high-content screening assay. The apoptotic rate and the expression of cleaved caspase-8 and -3 in addition to the cleaved poly(ADP-ribose) polymerase in SHG44 cells significantly increased in the TRAIL-overexpressing EPC treatment group compared with the controls. The increased apoptotic rate was reversed using a caspase inhibitor. The findings suggested that the TRAIL-expressing EPCs induced apoptosis in the SHG44 cells by activating the death receptor pathway, indicating that the TRAIL-expressing EPCs may be a useful strategy for glioma treatment.
胶质瘤是中枢神经系统中最常见的侵袭性神经上皮恶性肿瘤之一。它具有高复发率和不良预后，主要原因是新型治疗药物无法穿透血脑屏障（BBB）。据报道，内皮祖细胞（EPCs）可穿过血脑屏障并到达肿瘤部位。然而，表达肿瘤坏死因子相关凋亡诱导配体（TRAIL）的EPCs是否能诱导胶质瘤细胞凋亡尚需进一步研究。在本研究中，通过慢病毒感染将EPCs转染并使其稳定表达TRAIL。研究了这些表达TRAIL的EPCs对SHG44胶质瘤细胞系的促凋亡作用。通过高内涵筛选分析，研究了表达TRAIL的EPCs通过Transwell培养系统向SHG44细胞的迁移能力。与对照组相比，TRAIL过表达EPC治疗组中SHG44细胞的凋亡率、裂解的半胱天冬酶-8和-3以及裂解的聚（ADP-核糖）聚合酶的表达显著增加。使用半胱天冬酶抑制剂可逆转凋亡率的增加。这些发现表明，表达TRAIL的EPCs通过激活死亡受体途径诱导SHG44细胞凋亡，这表明表达TRAIL的EPCs可能是一种治疗胶质瘤的有效策略。
