Abstract

Abstract Glioblastoma (GB) is the most common malignant brain tumor and is characterized by high invasiveness, poor prognosis, and limited therapeutic options. Studies silencing the gene expression using interference RNA tool (siRNA) have been proposed as new alternative for cancer therapy. Here, we evaluated the potential of CD73 as a new therapeutic target, because it is overexpressed in solid tumors and emerges as a promising target to control GB progression. A cationic nanoemulsion (NE) as siRNA-CD73 delivery system was developed and its effect on glioma growth was determined. The nanostructured system was effective to complex the oligonucleotides for delivering on target cells. In addition, we observed that the NE-siRNA-CD73 complex was effective to reduce CD73 protein levels and AMPase activity which was further related to decreased in vitro C6 glioma cell viability. In addition, blockade of CD73 by NE-siRNA CD73 delayed in vivo tumor growth in a preclinical glioblastoma model by inducing apoptosis. Meanwhile, significantly reduced the population of lymphocytes, particularly Tregs, which could be associated to the antiglioma effect induced by the treatment. The data indicate the potential of siRNA-CD73 loaded cationic nanoemulsion as a therapeutic alternative to glioma treatment. Citation Format: Fernanda Cardoso Teixeira, Juliana H Azambuja, Helder F Teixeira, ELIZANDRA BRAGANHOL. CD73 as a new target for glioblastoma therapy [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr B131. doi:10.1158/1535-7163.TARG-19-B131

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