Temozolomide is additive with cytotoxic effect of irradiation in canine glioma cell lines

Abstract Background Similar to human glioblastoma patients, glial tumours in dogs have high treatment resistance and a guarded prognosis. In human medicine, the addition of temozolomide to radiotherapy leads to a favourable outcome in vivo as well as a higher antiproliferative effect on tumour cells...

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Autores principales:	Nina Simona Tresch, Daniel Fuchs, Luca Morandi, Caterina Tonon, Carla Rohrer Bley, Katarzyna J. Nytko
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	brain tumour chemoradiation dog in vitro O‐6‐methylguanine‐DNA methyltransferase (MGMT) Veterinary medicine SF600-1100
Acceso en línea:	https://doaj.org/article/c491c22a2201430a9e482953be6be5db
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spelling	oai:doaj.org-article:c491c22a2201430a9e482953be6be5db2021-11-19T17:14:25ZTemozolomide is additive with cytotoxic effect of irradiation in canine glioma cell lines2053-109510.1002/vms3.620https://doaj.org/article/c491c22a2201430a9e482953be6be5db2021-11-01T00:00:00Zhttps://doi.org/10.1002/vms3.620https://doaj.org/toc/2053-1095Abstract Background Similar to human glioblastoma patients, glial tumours in dogs have high treatment resistance and a guarded prognosis. In human medicine, the addition of temozolomide to radiotherapy leads to a favourable outcome in vivo as well as a higher antiproliferative effect on tumour cells in vitro. Objectives The aim of the study was to determine the radio‐ and temozolomide‐sensitivity of three canine glial tumour cell lines and to investigate a potential additive cytotoxic effect in combined treatment. Additionally, we wanted to detect the level of MGMT promoter methylation in these cell lines and to investigate a potential association between MGMT promoter methylation and treatment resistance. Methods Cells were treated with various concentrations of temozolomide and/or irradiated with 4 and 8 Gy. Radiosensitization by temozolomide was evaluated using proliferation assay and clonogenic assay, and MGMT DNA methylation was investigated using bisulfite next‐generation sequencing. Results In all tested canine cell lines, clonogenicity was inhibited significantly in combined treatment compared to radiation alone. All canine glial cell lines tested in this study were found to have high methylation levels of MGMT promoter. Conclusions Hence, an additive effect of combined treatment in MGMT negative canine glial tumour cell lines in vitro was detected. This motivates to further investigate the association between treatment resistance and MGMT, such as MGMT promoter methylation status.Nina Simona TreschDaniel FuchsLuca MorandiCaterina TononCarla Rohrer BleyKatarzyna J. NytkoWileyarticlebrain tumourchemoradiationdogin vitroO‐6‐methylguanine‐DNA methyltransferase (MGMT)Veterinary medicineSF600-1100ENVeterinary Medicine and Science, Vol 7, Iss 6, Pp 2124-2134 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	brain tumour chemoradiation dog in vitro O‐6‐methylguanine‐DNA methyltransferase (MGMT) Veterinary medicine SF600-1100
spellingShingle	brain tumour chemoradiation dog in vitro O‐6‐methylguanine‐DNA methyltransferase (MGMT) Veterinary medicine SF600-1100 Nina Simona Tresch Daniel Fuchs Luca Morandi Caterina Tonon Carla Rohrer Bley Katarzyna J. Nytko Temozolomide is additive with cytotoxic effect of irradiation in canine glioma cell lines
description	Abstract Background Similar to human glioblastoma patients, glial tumours in dogs have high treatment resistance and a guarded prognosis. In human medicine, the addition of temozolomide to radiotherapy leads to a favourable outcome in vivo as well as a higher antiproliferative effect on tumour cells in vitro. Objectives The aim of the study was to determine the radio‐ and temozolomide‐sensitivity of three canine glial tumour cell lines and to investigate a potential additive cytotoxic effect in combined treatment. Additionally, we wanted to detect the level of MGMT promoter methylation in these cell lines and to investigate a potential association between MGMT promoter methylation and treatment resistance. Methods Cells were treated with various concentrations of temozolomide and/or irradiated with 4 and 8 Gy. Radiosensitization by temozolomide was evaluated using proliferation assay and clonogenic assay, and MGMT DNA methylation was investigated using bisulfite next‐generation sequencing. Results In all tested canine cell lines, clonogenicity was inhibited significantly in combined treatment compared to radiation alone. All canine glial cell lines tested in this study were found to have high methylation levels of MGMT promoter. Conclusions Hence, an additive effect of combined treatment in MGMT negative canine glial tumour cell lines in vitro was detected. This motivates to further investigate the association between treatment resistance and MGMT, such as MGMT promoter methylation status.
format	article
author	Nina Simona Tresch Daniel Fuchs Luca Morandi Caterina Tonon Carla Rohrer Bley Katarzyna J. Nytko
author_facet	Nina Simona Tresch Daniel Fuchs Luca Morandi Caterina Tonon Carla Rohrer Bley Katarzyna J. Nytko
author_sort	Nina Simona Tresch
title	Temozolomide is additive with cytotoxic effect of irradiation in canine glioma cell lines
title_short	Temozolomide is additive with cytotoxic effect of irradiation in canine glioma cell lines
title_full	Temozolomide is additive with cytotoxic effect of irradiation in canine glioma cell lines
title_fullStr	Temozolomide is additive with cytotoxic effect of irradiation in canine glioma cell lines
title_full_unstemmed	Temozolomide is additive with cytotoxic effect of irradiation in canine glioma cell lines
title_sort	temozolomide is additive with cytotoxic effect of irradiation in canine glioma cell lines
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/c491c22a2201430a9e482953be6be5db
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Temozolomide is additive with cytotoxic effect of irradiation in canine glioma cell lines

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