Evaluation of Single and Combined Temozolomide and Doxorubicin Treatment Responses in Low- and High-Grade Glioma In Vitro

TL;DR

This study evaluates how low- and high-grade glioma cells respond to single and combined treatments with temozolomide and doxorubicin in laboratory experiments.

Contribution

The study provides new insights into the cytotoxic effects of temozolomide and doxorubicin in low- and high-grade glioma cell lines, including their resistance patterns and lack of synergy in combination.

Findings

GB1B (high-grade) cells were more sensitive to doxorubicin than AC1B (low-grade) cells at 7- and 10-day exposure.

GB1B cells became more resistant to doxorubicin at 14 days compared to AC1B cells.

GB1B cells showed greater resistance to temozolomide than AC1B cells, with resistance increasing over time.

Abstract

Background: Astrocytoma, the most common type of glioma, can histologically be low or high grade. Treatment recommendations for astrocytic tumors are based on the histopathological and molecular phenotype. For grade 2 astrocytoma, the combination of radiotherapy and adjuvant chemotherapy with procarbazine, lomustine, and vincristine (PCV) is better than radiotherapy alone. Temozolomide (TMZ) is being increasingly recognized as a replacement for PCV in brain tumor therapy, due to the lower myelotoxicity. TMZ is currently a well-established first-line treatment for grade 3 astrocytoma, grade 4 astrocytoma, and glioblastoma and it is also sporadically used for grade 2 astrocytoma. However, TMZ faces multiple challenges such as adverse effects and drug resistance.

Methods: In this study, we compared the cytotoxic effect induced by TMZ and doxorubicin (DOXO), alone and in combination, on a low-grade astrocytoma cell line (AC1B) and a high-grade glioma cell line (GB1B).

Results: We found that TMZ and DOXO, each produced a cytotoxic effect in monotherapy. GB1B cell line was more sensitive to the treatment than AC1B cells, at a 7- and 10-day exposure to the DOXO. However, when the duration of the treatment was extended to 14 days, GB1B cells became more resistant to DOXO treatment, compared to AC1B cells. Regarding the treatment with TMZ, GB1B exhibited greater resistance to TMZ compared to AC1B, across all studied intervals and the resistance to treatment of GB1B increased with longer exposure time. However, in combined therapy, the drugs did not exert a synergistic effect on any astrocytic cell line.

Conclusions: The current data suggest that both TMZ and DOXO exhibit efficient therapeutic effects on low- and high-grade glioma cells. However, no synergistic effect was observed for combined therapy.

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