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The role of apoptotic cell death in the radiosensitising effect of gemcitabine

BACKGROUND: The aim of this study was to evaluate the radiosensitising effect of gemcitabine, in terms of cell-cycle progression, induction of apoptosis, and to investigate the molecular events regulating apoptosis. METHODS: Tumour cells were treated with gemcitabine, radiation, or the combination....

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Autores principales: Pauwels, B, Vermorken, J B, Wouters, A, Ides, J, Van Laere, S, Lambrechts, H A J, Pattyn, G G O, Vermeulen, K, Meijnders, P, Lardon, F
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2736812/
https://www.ncbi.nlm.nih.gov/pubmed/19672265
http://dx.doi.org/10.1038/sj.bjc.6605145
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author Pauwels, B
Vermorken, J B
Wouters, A
Ides, J
Van Laere, S
Lambrechts, H A J
Pattyn, G G O
Vermeulen, K
Meijnders, P
Lardon, F
author_facet Pauwels, B
Vermorken, J B
Wouters, A
Ides, J
Van Laere, S
Lambrechts, H A J
Pattyn, G G O
Vermeulen, K
Meijnders, P
Lardon, F
author_sort Pauwels, B
collection PubMed
description BACKGROUND: The aim of this study was to evaluate the radiosensitising effect of gemcitabine, in terms of cell-cycle progression, induction of apoptosis, and to investigate the molecular events regulating apoptosis. METHODS: Tumour cells were treated with gemcitabine, radiation, or the combination. 0–72 h after treatment, cells were collected for cell-cycle analysis and apoptosis determination. Caspase 8 and 9, Bid and tBid expression were determined by western blot. The mitochondrial membrane potential was determined using flow cytometry. An RT(2) Profiler PCR Array for human apoptotic genes was performed after the combination or TRAIL treatment. RESULTS: Gemcitabine and radiation resulted in an early S-phase block immediately after treatment, after which the cells moved synchronously through the cell cycle. When cell-cycle distribution returned to pre-treatment levels, an increased induction of apoptosis was observed with activation of caspase 8 and 9 and a reduction of the mitochondrial membrane potential. Gene expression after treatment with radiosensitising conditions was comparable with expression after the TRAIL treatment. CONCLUSION: A role for the cell-cycle perturbations and the induction of apoptosis could be attributed to the radiosensitising effect of gemcitabine. Apoptosis induction was comparable with the apoptotic pathway observed after the TRAIL treatment, that is the involvement of the extrinsic apoptosis pathway.
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spelling pubmed-27368122010-08-18 The role of apoptotic cell death in the radiosensitising effect of gemcitabine Pauwels, B Vermorken, J B Wouters, A Ides, J Van Laere, S Lambrechts, H A J Pattyn, G G O Vermeulen, K Meijnders, P Lardon, F Br J Cancer Translational Therapeutics BACKGROUND: The aim of this study was to evaluate the radiosensitising effect of gemcitabine, in terms of cell-cycle progression, induction of apoptosis, and to investigate the molecular events regulating apoptosis. METHODS: Tumour cells were treated with gemcitabine, radiation, or the combination. 0–72 h after treatment, cells were collected for cell-cycle analysis and apoptosis determination. Caspase 8 and 9, Bid and tBid expression were determined by western blot. The mitochondrial membrane potential was determined using flow cytometry. An RT(2) Profiler PCR Array for human apoptotic genes was performed after the combination or TRAIL treatment. RESULTS: Gemcitabine and radiation resulted in an early S-phase block immediately after treatment, after which the cells moved synchronously through the cell cycle. When cell-cycle distribution returned to pre-treatment levels, an increased induction of apoptosis was observed with activation of caspase 8 and 9 and a reduction of the mitochondrial membrane potential. Gene expression after treatment with radiosensitising conditions was comparable with expression after the TRAIL treatment. CONCLUSION: A role for the cell-cycle perturbations and the induction of apoptosis could be attributed to the radiosensitising effect of gemcitabine. Apoptosis induction was comparable with the apoptotic pathway observed after the TRAIL treatment, that is the involvement of the extrinsic apoptosis pathway. Nature Publishing Group 2009-08-18 2009-08-11 /pmc/articles/PMC2736812/ /pubmed/19672265 http://dx.doi.org/10.1038/sj.bjc.6605145 Text en Copyright © 2009 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Translational Therapeutics
Pauwels, B
Vermorken, J B
Wouters, A
Ides, J
Van Laere, S
Lambrechts, H A J
Pattyn, G G O
Vermeulen, K
Meijnders, P
Lardon, F
The role of apoptotic cell death in the radiosensitising effect of gemcitabine
title The role of apoptotic cell death in the radiosensitising effect of gemcitabine
title_full The role of apoptotic cell death in the radiosensitising effect of gemcitabine
title_fullStr The role of apoptotic cell death in the radiosensitising effect of gemcitabine
title_full_unstemmed The role of apoptotic cell death in the radiosensitising effect of gemcitabine
title_short The role of apoptotic cell death in the radiosensitising effect of gemcitabine
title_sort role of apoptotic cell death in the radiosensitising effect of gemcitabine
topic Translational Therapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2736812/
https://www.ncbi.nlm.nih.gov/pubmed/19672265
http://dx.doi.org/10.1038/sj.bjc.6605145
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