Title
The role of apoptotic cell death in the radiosensitising effect of gemcitabine The role of apoptotic cell death in the radiosensitising effect of gemcitabine
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
London ,
Subject
Human medicine
Source (journal)
The British journal of cancer. - London
Volume/pages
101(2009) , p. 628-636
ISSN
0007-0920
ISI
000268861000012
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
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. 072 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 RT2 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.
E-info
https://repository.uantwerpen.be/docman/iruaauth/397598/d182c4c4db4.pdf
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