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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Radiosensitization by thymidine phosphorylase inhibitor in thymidine phosphorylase negative and overexpressing bladder cancer cell lines
Nucleosides, Nucleotides and Nucleic Acids, Volume 33, No. 4-6, Year 2014
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Description
TAS-102 (trifluorothymidine [TFT] and thymidine phosphorylase inhibitor [TPI] in a molar ratio of 1:0.5) has activity in 5-fluorouracil resistant colon cancer. TPI is added to increase TFT's bioavailability. TFT has a dual mechanism of action by inhibiting thymidylate synthase and by its incorporation into DNA. Interesting radiosensitizing effects of TPI were recently reported. The aim of our study was to determine whether TP expression would affect radiosensitivity and to characterize the effect of TPI. Two bladder cancer cell lines RT112 (TP negative) and RT112/TP (TP overexpression) were tested for drug sensitivity and radiosensitivity (clonogenic assay), with and without TFT and/or TPI. Expression of γ H2AX was used as marker for DNA damage. RT112 cells were not more sensitive to TFT then RT112/TP cells. TPI alone did not inhibit cell growth of RT112 even at 100 M, but inhibited that of RT112/TP by 27%. In both RT112 and RT112/TP cells 10 M TPI did not or slightly affect radiosensitivity, but 100 M TPI alone enhanced the radiation response (p <.05). TFT alone at 1 M and in combination with 10 M TPI did not affect the radiation response of both cell lines. TPI alone induced expression of ΥH2AX, which was increased in combination with radiation. In conclusion, TPI enhanced radiosensitivity at high concentrations, independent of TP expression, while TFT and TPI at a low concentration did not affect the radiosensitivity of RT112 and RT112/TP cell lines. © 2014 Taylor and Francis Group, LLC.
Authors & Co-Authors
El-Naggar, Maha
Egypt, Asyut
Assiut University
Netherlands, Amsterdam
Amsterdam Umc - Vrije Universiteit Amsterdam
Ebbing, Eva
Netherlands, Amsterdam
Amsterdam Umc - Vrije Universiteit Amsterdam
Bijnsdorp, Irene
Netherlands, Amsterdam
Amsterdam Umc - Vrije Universiteit Amsterdam
Van Den Berg, Jaap
Netherlands, Amsterdam
Amsterdam Umc - Vrije Universiteit Amsterdam
Peters, Godefridus J.
Netherlands, Amsterdam
Amsterdam Umc - Vrije Universiteit Amsterdam
Statistics
Citations: 9
Authors: 5
Affiliations: 2
Identifiers
Doi:
10.1080/15257770.2014.892127
e-ISSN:
15322335
Research Areas
Cancer
Genetics And Genomics