In vitro repositioning therapy with olaparib, temozolomide and oxaliplatin in glioblastoma cell lines: U118, U87, U251, H4 and human fibroblasts.

BACKGROUND

Central nervous system (CNS) tumors, including gliomas, are among the most aggressive cancers, with glioblastoma multiforme (GBM) being the most common and lethal. This study explores the potential of multidrug repositioning as a modern chemotherapy strategy for GBM cell lines. It combines the standard GBM chemotherapeutic temozolomide (TMZ) with olaparib (OLA) and oxaliplatin (OXA), both repurposed from other cancer types. Most experimental drug therapy studies focus on just one or two selected high-grade GBM cell lines, but in this study, four such cell lines were used.

METHODS

Glioblastoma (GBM) cell lines U118 MG, H4, U251 MG and U87 MG were treated for 72 h with oxaliplatin (OXA, 50-200 µM), olaparib (OLA, 1-100 µM), or temozolomide (TMZ, 10-100 µM). Cell viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2 H-tetrazolium (MTS) assay. Half-maximal inhibitory concentration (IC₅₀) values were calculated using GraphPad Prism 8. A human fibroblast line (hFib) from a healthy donor was used as a control. The type of cell death following the above treatments was analysed using a fluorescence-based Apoptotic, Necrotic & Healthy Cells Quantification Kit.

RESULTS

The combination of OLA, OXA, and TMZ significantly reduced cell viability and survival, inducing apoptosis/necrosis more effectively than TMZ alone. These synergistic effects alter glioblastoma metabolism, promote apoptosis, and enhance antitumor activity in vitro.

CONCLUSIONS

The proposed multidrug repositioning chemotherapy produced a therapeutic effect at lower doses, suggesting that it is potentially a safer and more effective treatment option.