Stefana Oana Purcaru
University of Medicine and Pharmacy of Craiova, Romania
Title: Targeted angiogenic receptors in low passage glioblastoma cell lines in vitro
Biography
Biography: Stefana Oana Purcaru
Abstract
The failure of therapies targeting tumor angiogenesis may be caused by anti-angiogenic resistance mechanisms induced by VEGF and non-VEGF pathways alterations. Several studies confirmed the association between tumor heterogeneity and response to treatment. It is well known from literature that immortal glioblastoma (GB) cell lines fail to reproduce the in vivo tumor heterogeneity and shown to accumulate mutations that may produce changes in the cell genotype and phenotype that have not initially been detected at earlier passages. Low-passage primary cultures may better reflect the properties of original tumor and are considered much more relevant models for studying the malignant diseases in vitro. The aim of this study is to evaluate the effect of angiogenesis inhibitors in low-passage primary GB cultures in vitro. The cells line was established from freshly sample of brain tumor tissue, was cultured in standard conditions and frozen after passage three. After thawing in standard conditions, adherent monolayer cells showed continuous growth and could recover. Cells were treated with angiogenesis inhibitors and the viability was evaluated by using MTT assay and by hemocytometric counting. The treatment with AG1433 (a PDGFRβ inhibitor), SU1498 (a VEGFR2 inhibitor) and ELTD1siRNA induced cytotoxicity in glioblastoma cells. BEZ235, a dual PI3K/mTOR inhibitor, induced cell death to the same extent as ELTD1siRNA but caused a greater degree of cytotoxicity than AG1433 and SU1498. The findings expand our understanding of the evaluation of angiogenesis inhibition in vitro and support the use of low-passage GB cell lines as preclinical models.