The balance among radiation-induced cell death pathways in the p53-mutant human glioblastoma cell line T98G: A preliminary study

The specific contributions of apoptosis, necrosis, autophagy, and cellular senescence pathways in malignant tumor cells (especially p-53 defective or mutated tumors) are unclear. We evaluated the cell viability, apoptosis, autophagic cell death, and cell senescence of T98G cells irradiated with 6 megavoltage (MV) X-rays at 0, 2, 4, and 8 Gy. The cell-death rate obtained by a colony formation assay was used to derive the cell-surviving fraction at each irradiation dose. We evaluated the relative balance between each irradiation dose and the cell-death pathway by a four-dimensional (4D) plot generated by incorporating the cell-death rate, autophagic cell death, and cell senescence. A dose-dependent decrease in the cell-survival rate was observed, with no significant apoptosis induction at any dose. Autophagic cell death and cellular senescence both exhibited dose-dependent increases, with autophagy dominating at 2-4 Gy and senescence more prominent at 8 Gy. The complex relationships among apoptosis, autophagy, and senescence in T98G remain unresolved. Our results highlight the dose-dependent shifts in autophagy and senescence, providing a foundational understanding of cell-death dynamics in radiation-resistant tumors and perhaps paving the way for novel strategies that exploit these pathways to enhance glioblastoma treatments' efficacy.