Pro-apoptotic effect of TRAIL-transfected endothelial progenitor cells on glioma cells

摘要

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.