In vitro effects of mesenchymal stem cells and various agents on apoptosis of glioblastoma cells
Year: 2017
Type: article
Abstract: white matter tracts (11).Recurrence has also been attributed to genetic heterogeneity and the complex molecular pathology of GBM (20,29).Unfortunately, most systemic chemotherapeutics developed to treat GBM are ineffective because of their inability to cross the blood-brain barrier at certain doses without exerting systemic toxicity (31).Therefore, the treatment of malignant gliomas is one of the most difficult challenges in neuro-oncology.Recently, inspiring studies have found that targeted therapy that acts on specific signaling pathways that underlie uncontrolled cellular growth and induce apoptosis might be an effective and practical option for GBM treatment (13).Studies have also found that stem cells have tumor-specific homing properties and that programminggrade IV astrocytoma (9).It is the most common and most aggressive primary brain tumor, accounting for approximately 60%-75% of all astrocytomas and 12%-15% of all intracranial tumors (27).The current treatment protocol for GBM is maximal safe surgical resection, radiotherapy, and chemotherapy (48).Despite this aggressive medical strategy, GBMs are either refractory or resistant to treatment (44).Even if gross total resection is confirmed by magnetic resonance imaging, local GBM recurrences are common because of microscopic tumor infiltration along perivascular spaces and AIM: To investigate a new anti-tumor treatment method using stem cells transfected with specific genes and proteins that induce apoptosis in tumor cells. MATERIAL and METHODS:We used glioblastoma (GBM) cells and human adipose tissue-derived mesenchymal stem cells (AD-MSCs) in this study.The AD-MSCs were transfected with the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).To overcome apoptosis resistance in tumor cells, we used suberoylanilide hydroxamic acid (SAHA) as the histone deacetylase inhibitor and embelin as the X-linked inhibitor of apoptosis protein (XIAP).In addition, we silenced the XIAP gene on GBM cells with the shXIAP plasmid.Following the determination of half-maximal effective concentration (EC50%) doses of SAHA and embelin, GBM cells were incubated with them for 24 hours.XIAP-silenced and XIAP-non-silenced GBM cells were cultured with TRAIL-nontransfected and TRAIL-transfected stem cells for 24 hours.Viability and cell cycle analysis of all groups were determined using annexin V/propidium iodide and cell cycle method via flow cytometry.RESULTS: TRAIL-transfected AD-MSCs, XIAP silencing, embelin, and SAHA induced apoptosis in GBM cells and decreased their proliferation, whereas TRAIL-non-tranfected AD-MSCs did not.CONCLUSION: Engineered stem cell therapies and molecular studies show promise in developing combination therapies for effective treatment of GBM.
Source: Turkish Neurosurgery
Institutions: Acıbadem University, Marmara University
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funder: Marmara Üniversitesi
OpenAlex ID: W2777049242