Valproic acid and celecoxib enhance the effect of temozolomide on glioblastoma cells

Objective. To evaluate the survival of patients with recurrent glioblastoma receiving valproic acid and to study its impact in combination with temozolomide and celecoxib on tumor cells. Materials and methods. A retrospective analysis was conducted on data from patients diagnosed with glioblastoma (ICD-10 – C71) who received valproic acid as part of their comprehensive treatment and were reoperated on with recurrent glioblastoma. Tumor cells of the C6, U87 and T98G lines were used for the experimental study. Glioblastoma modeling was performed using Wistar rats. The study was approved by the ethics committee. Results. The median overall survival of patients with glioblastoma receiving valproic acid accounted for 22 months, compared to 13 months for patients not receiving valproic acid. In in vitro experiments, the half-maximal inhibitory concentration (IC50) of temozolomide for various tumor cell lines ranged from 435.3 to 844 μM; the IC50 of valproic acid for U87MG, T98G, and C6 cell lines comprised 1510, 3900, and 3600 μM, respectively; the IC50 of celecoxib for these tumor cell lines amounted to 30.1, 41.07, and 48.4 μM, respectively. Valproic acid significantly enhanced the antiglioma effect of temozolomide on U87 cell lines; the highest sensitivity to the action of celecoxib in combination with temozolomide was observed in C6 and T98G cell lines. The combination of valproic acid with celecoxib enhanced the antiglioma action of temozolomide both in vitro and in vivo, which was accompanied by a reduction in tumor volume (p < 0.05) and increased survival of experimental animals. Conclusion. The high antiglioma potential of the combination of valproic acid and celecoxib with temozolomide opens up prospects for optimizing existing treatment approaches for recurrent glioblastoma, thereby highlighting the need for further research. Valproic acid and celecoxib enhance the effects of temozolomide on glioblastoma cells.