The Effectiveness of Multidrug Chemotherapy with Olaparib, Temozolomide and Oxaliplatin Compared to Radiotherapy in Glioblastoma Multiforme in Vitro Models and Human Fibroblasts

Introduction : Glioblastoma multiforme (GBM) remains one of the most treatment-resistant central nervous system (CNS) tumors. This study evaluated the efficacy of multidrug repositioning combining oxaliplatin (OXA), olaparib (OLA), and temozolomide (TMZ), administered alone or in combination with photon radiotherapy, in GBM cell lines as in vitro models. Methods U118 MG and U87 MG cells, as well as control human fibroblasts (hFib) from a healthy donor, were treated with OXA (50–200 µM), OLA (1-100 µM), and TMZ (10–100 µM), alone and in combination. Cell viability was assessed after 72 hours using the MTS assay, and apoptosis/necrosis was quantified using a fluorescent apoptosis, necrosis, and healthy cell quantification kit. Treatments were tested with (2 Gy, 4 Gy) and without irradiation. Results Radiotherapy significantly enhanced the cytotoxic effects of all drugs, with the strongest reductions in viability observed for multidrug combinations. The addition of 2 Gy and 4 Gy irradiation markedly enhanced the activity of OLA + TMZ, OXA + TMZ, and OLA + OXA, leading to substantial loss of GBM cell viability. The greatest synergistic response has been observed with the triple drug combination (OLA + OXA + TMZ) plus radiotherapy, which produced extensive necrosis across all GBM models used. Conclusions The combination of OXA, OLA, and TMZ, especially when combined with photon radiotherapy, demonstrates potential synergistic cytotoxicity in GBM while sparing healthy fibroblasts. These results support the use of multidrug combination chemotherapy with radiotherapy as a promising and potentially safer treatment strategy for GBM.