Specificity of U2 and GOL1 aptamers to EGFR-positive human glioblastoma cells in vitro

Abstract

Overexpression of the epidermal growth factor receptor (EGFR) or its mutations mediate signaling pathways leading to proliferation, invasion of tumor cells, as well as to an increase in their survival. Despite the success of the clinical use of antibodies against EGFR in patients with colorectal cancer and squamous cell carcinoma of the head and neck, their low effectiveness in glioblastoma has been shown. Therefore, for the treatment of gliomas, a specific EGFR drug is needed, capable of penetrating into the tumor focus in the brain, and having low immunogenicity. In this work, aptamers – single-stranded DNA oligonucleotides specific to EGFR, U2 and Gol1 are presented as such a preparation. In this study, we obtained a cellular model of human glioma with EGFR and EGFRvIII overexpression, which showed the specificity of U2 and Gol1 aptamers to these receptors using classical methods, as well as the method of aptaimmunocytochemistry. A study of the effect of binding of the Gol1 aptamer to the EGFRvIII receptor on the next steps of the signaling pathway showed a change in the expression levels of genes associated with cell proliferation and survival (JUN, FOS, CCND1, PI3K and AKT3), while the U2 aptamer did not demonstrate a significant effect on cells in vitro. These results showed that the Gol1 aptamer has therapeutic potential against human glioblastoma tumor cells overexpressing the EGFRvIII mutant type receptor.