Comparison of 3D and 2D cultures for evaluating the effect of combination therapy with Erlotinib and Imatinib on Glioblastoma multiforme

Abstract

Abstract Purpose Glioblastoma multiforme (GBM) is a common brain tumor with aggressive phenotypes and resistance to treatments. Erlotinib and Imatinib, combined, hold promise as innovative therapies to overcome GBM's heterogeneous malignancy. This study conducted experiments in two-dimensional (2D) and three-dimensional (3D) cell cultures, comparing them to the in vivo microenvironment. Methods The study measured the effects of Imatinib and Erlotinib on the survival of 2D and 3D cell cultures and apoptosis after 24 and 48 hours (h) post-treatment using MTT assay and flow cytometry. The study also investigated gene expression of Bcl-2 and VEGF using qRT-PCR. The scratch test was used to explore drug treatments' effects on cellular migration. Results Based on our results, combination therapy reduced tumor cell migration by reducing Bcl-2 and VEGF gene expression through Erlotinib, Imatinib, or combination therapy. However, combination therapy showed a more significant reduction in B-cl2 gene expression than single therapy, as opposed to VEGF expression. The apoptotic effect of combination therapy was confirmed, with an increase in death percentage in the 48h-3D treated group (*P < 0.05 for monotherapy and ***P < 0.001 for combination). Conclusion 3D culture offers a more physiological environment for studying oncolytic drug effects. In a 3D in vitro study, combination GBM therapy caused significant apoptosis, requiring further preclinical model studies.