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

Autor:	Staicu GA; Department of Biochemistry, University of Medicine and Pharmacy of Craiova, Craiova, ROU., Tataranu LG; Department of Neurosurgery, Bagdasar-Arseni Clinical Emergency Hospital, Bucharest, ROU.; Department of Neurosurgery, Carol Davila University of Medicine and Pharmacy, Bucharest, ROU., Tache DE; Department of Biochemistry, University of Medicine and Pharmacy of Craiova, Craiova, ROU., Popescu SO; Department of Biochemistry, University of Medicine and Pharmacy of Craiova, Craiova, ROU., Artene SA; Department of Biochemistry, University of Medicine and Pharmacy of Craiova, Craiova, ROU., Danoiu S; Department of Physiology, University of Medicine and Pharmacy of Craiova, Craiova, ROU., Sfredel V; Department of Physiology, University of Medicine and Pharmacy of Craiova, Craiova, ROU., Barcan EN; Department of Biochemistry, University of Medicine and Pharmacy of Craiova, Craiova, ROU., Baloi SC; Department of Biochemistry, University of Medicine and Pharmacy of Craiova, Craiova, ROU., Dricu A; Department of Biochemistry, University of Medicine and Pharmacy of Craiova, Craiova, ROU.
Jazyk:	angličtina
Zdroj:	Cureus [Cureus] 2024 Aug 15; Vol. 16 (8), pp. e66928. Date of Electronic Publication: 2024 Aug 15 (Print Publication: 2024).
DOI:	10.7759/cureus.66928
Abstrakt:	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. Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. The Commission of Scientific Ethics and Deontology - University of Medicine and Pharmacy of Craiova issued approval 25/18.07.2011. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: This research was funded by Grants PN-III-P4-ID-PCE-2020-1649 and PN-II-ID-PCE-2011-3-1041 from the UEFISCDI. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. (Copyright © 2024, Staicu et al.)
Databáze:	MEDLINE
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