Synergistic Effects of Temozolomide and Doxorubicin in the Treatment of Glioblastoma Multiforme: Enhancing Efficacy through Combination Therapy

Abstract

Glioblastoma multiforme (GBM), a grade IV (WHO classification) malignant brain tumor, poses significant challenges in treatment. The current standard treatment involves surgical tumor removal followed by radiation and chemotherapeutic interventions. However, despite these efforts, the median survival for GBM patients remains low. Temozolomide, an alkylating agent capable of crossing the blood–brain barrier, is currently the primary drug for GBM treatment. Its efficacy, however, is limited, leading to the exploration of combination treatments. In this study, we have investigated the synergistic effects of combining temozolomide with doxorubicin, a chemotherapeutic agent widely used against various cancers. Our experiments, conducted on both temozolomide-sensitive (U87) and -resistant cells (GBM43 and GBM6), have demonstrated a synergistic inhibition of brain cancer cells with this combination treatment. Notably, the combination enhanced doxorubicin uptake and induced higher apoptosis in temozolomide-resistant GBM43 cells. The significance of our findings lies in the potential application of this combination treatment, even in cases of temozolomide resistance. Despite doxorubicin’s inability to cross the blood–brain barrier, our results open avenues for alternative delivery methods, such as conjugation with carriers like albumin or local administration at the surgical site through a hydrogel application system. Our study suggests that the synergistic interaction between temozolomide and doxorubicin holds promise for enhancing the efficacy of glioblastoma treatment. The positive outcomes observed in our experiments provide confidence in considering this strategy for the benefit of patients with glioblastoma.