Radiotherapy Resistance of 3D Bioprinted Glioma via ITGA2/P-AKT Signaling Pathway.

Abstract

Radiation therapy serves as the primary and widely employed adjuvant treatment following surgical intervention for malignant glioma of the brain. However, due to the inherent radiation tolerance of tumors, patients frequently encounter tumor recurrence and malignant progression within the radiation target area, ultimately succumbing to treatment ineffectiveness. The precise mechanism underlying radiation tolerance remains elusive due to the dearth of in vitro models and the limitations associated with animal models. Therefore, we engineered a 3D bioprinted glioma model, characterized the phenotypic traits of 3D-cultured glioma models in vitro, and assessed the radiation tolerance of 3D models in comparison to 2D glioma models when subjected to X-ray radiation. By comparing the differential gene expression profiles between the 2D and 3D glioma model, identify functional genes, and analyze distinctions in gene expression patterns with the aim of pinpointing functional genes. Relative to 2D models, the 3D glioma models exhibited substantial alterations in the expression of genes associated with the stromal microenvironment, notably a significant increase in the radiation tolerance gene ITGA2 (integrin subunit A2). In 3D glioma models, the knockdown of ITGA2 via shRNA resulted in reduced radiation tolerance in glioma cells and concomitant inhibition of the p-AKT pathway. Overall, in comparison to 2D models, the 3D bioprinted glioma model faithfully recapitulates the in vivo tumor microenvironment (TME) and exhibits enhanced resistance to radiation, mediated through the ITGA2/p-AKT pathway. This model represents a superior in vitro platform for investigating glioma radiotherapy tolerance. This article is protected by copyright. All rights reserved.