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Silencing of epidermal growth factor, latrophilin and seven transmembrane domain-containing protein 1 (ELTD1) via siRNA-induced cell death in glioblastoma
- Source :
- Journal of immunoassayimmunochemistry. 38(1)
- Publication Year :
- 2016
-
Abstract
- The failure of therapies targeting tumor angiogenesis may be caused by anti-angiogenic resistance mechanisms induced by VEGF and non-VEGF pathways alterations. Anti-angiogenic therapy failure is also attributed to immune system, acting by tumor-associated macrophages that release pro-angiogenic factors and a consequent increase of blood vessels. Recently, in a study by Rheal et al., a new angiogenic receptor, epidermal growth factor, latrophilin, and 7 trans-membrane domain-containing protein 1 on chromosome 1(ELTD1) has been identified as a promising glioma biomarker. In this study we aim to analyse whether this receptor may be used as a target molecule in glioblastoma therapy. Our results showed that small interfering RNA silencing ELTD1 caused cytotoxicity in glioblastoma cells. We also found that PDGFR, VEGFR, and their common PI3K/mTOR intracellular pathway inactivation-induced cytotoxicity in glioblastoma cells. Further, we found high percent of cytotoxicity in a low passage glioblastoma cell line after BEZ235 (a dual inhibitor of PI3K/mTOR pathway) treatment at nanomolar concentrations, compared to AG1433 (a PDGFR inhibitor) and SU1498 (a VEGFR inhibitor) that were only cytotoxic at micromolar ranges. In the future, these could prove as attractive therapeutic targets in single therapy or coupled with classic therapeutic approaches such as chemotherapy of radiotherapy.
- Subjects :
- 0301 basic medicine
Small interfering RNA
Receptors, Peptide
Clinical Biochemistry
Immunology
Biology
Receptors, G-Protein-Coupled
03 medical and health sciences
Epidermal growth factor
Glioma
medicine
Biomarkers, Tumor
Immunology and Allergy
Gene silencing
Humans
Gene Silencing
RNA, Small Interfering
Cytotoxicity
Receptor
PI3K/AKT/mTOR pathway
Cell Death
Epidermal Growth Factor
medicine.disease
Cell biology
Medical Laboratory Technology
030104 developmental biology
biology.protein
Cancer research
Glioblastoma
Platelet-derived growth factor receptor
Subjects
Details
- ISSN :
- 15324230
- Volume :
- 38
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of immunoassayimmunochemistry
- Accession number :
- edsair.doi.dedup.....56355747b0602cc1a4ee218748ca9bb3