Implication of the Androgen Receptor in Survival and Treatment Resistance in Glioblastoma Cells

Introduction: Glioblastoma is a highly aggressive brain tumor with limited therapeutic options. The androgen receptor (AR) has been shown to play a role in the progression of various cancers, but its involvement in glioblastoma remains unclear. This study aims to investigate the impact of testosterone, through AR activation, on cell viability and resistance to temozolomide, the main chemotherapeutic treatment for this disease.
The aim of the present work is to evaluate the effect of testosterone on cell viability in three glioblastoma cell lines (U87-MG, U118-MG, and A172), its interaction with temozolomide, and the identification of AR-regulated genes.

Methods: Cells were treated with testosterone (50 and 100 nM), in the presence or absence of bicalutamide (an AR antagonist) and/or temozolomide (60 µg/mL) for 24, 48, and 72 hours. Cell viability was assessed using the CCK-8 assay. Differential gene expression following testosterone exposure was analyzed by RNA sequencing and validated by RT-PCR.

Results: Testosterone exposure maintained or increased cell viability, an effect that was reversed by bicalutamide. Additionally, testosterone promoted resistance to temozolomide, particularly in U118-MG and A172 cell lines. RNA sequencing identified 7 commonly regulated genes across the three lines, of which NGFR and ANGPTL4 were associated with poorer prognosis in glioblastoma patients.

Conclusion : The androgen receptor plays a key role in survival and chemotherapy resistance in glioblastoma cell lines, mediated by the activation of specific genes such as NGFR and ANGPTL4. These findings suggest that AR inhibition could be a promising therapeutic strategy in glioblastoma.