Study of PTEN Gene Expression Changes in Glioblastoma Cells Following Chemotherapeutic Intervention

Glioblastoma (GBM) is one of the most aggressive and malignant primary tumors of the central nervous system (CNS), accounting for ۲۸% of all brain tumors and ۸۰% of malignant brain cases. GBM is highly invasive with a complex molecular and genetic heterogeneity, significantly affecting patient prognosis. Key signaling pathways such as PI۳K/Akt/mTOR and MAPK/ERK are involved in GBM progression. PTEN, a tumor suppressor gene, plays a critical role in negatively regulating the PI۳K/Akt/mTOR pathway, and its loss in GBM leads to enhanced tumor growth and resistance to therapy. This study investigates the effect of a pharmacological intervention on PTEN gene expression in glioblastoma cells to assess its therapeutic potential. in this project, Glioblastoma cells were obtained from the Medical Science University of Iran. After passaging, freezing, and counting, cells were treated with a chemotherapeutic agent at two concentrations: ۰.۵ µM and ۱ µM. Gene expression and apoptosis levels were assessed using qRT-PCR and flow cytometry. Apoptosis was measured by comparing the treated groups with control groups by Annexin V/PI method. The impact of the treatment on PTEN expression and cellular viability was also evaluated. Flow cytometry results indicated that treatment significantly increased both early and late apoptosis compared to the control group. Apoptosis increased from ۳.۹۴% in the control to ۳۲.۸۴% in the ۰.۵ µM group and ۴۸.۴% in the ۱ µM group (p < ۰.۰۰۰۱), showing a strong dose-dependent effect. Cell viability decreased from ۹۴.۶% in the control to ۶۶.۳% and ۵۰.۸% in the ۰.۵ µM and ۱ µM groups, respectively. Moreover, qRT-PCR results demonstrated a significant upregulation of PTEN expression in both treated groups. PTEN expression increased ۳.۵-fold in the ۰.۵ µM group and ۶-fold in the ۱ µM group compared to the control (p < ۰.۰۰۰۱), suggesting suppression of the PI۳K/Akt/mTOR pathway and induction of apoptosis. The treatment significantly enhanced PTEN expression and induced apoptosis in glioblastoma cells, indicating its potential as a therapeutic agent. The dose-dependent increase in apoptosis and PTEN expression highlights the importance of targeting the PI۳K/Akt/mTOR pathway in GBM treatment. Additionally, the upregulation of PTEN leads to the suppression of tumorigenesis pathways and enhances the inhibition of these pathways within the tumor, preventing cell growth, proliferation, and differentiation. These findings suggest that further exploration of this pharmacological intervention may provide a promising approach to improving GBM patient outcomes.

کلیدواژه ها:

Glioblastoma ، PTEN ، PI۳K/AKT/mTOR ، Actinomycin D