A radiosensitizing effect of RAD51 inhibition in glioblastoma stem-like cellsReportar como inadecuado




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BMC Cancer

, 16:604

Cell and molecular biology

Abstract

BackgroundRadioresistant glioblastoma stem cells GSCs contribute to tumor recurrence and identification of the molecular targets involved in radioresistance mechanisms is likely to enhance therapeutic efficacy. This study analyzed the DNA damage response following ionizing radiation IR in 10 GSC lines derived from patients.

MethodsDNA damage was quantified by Comet assay and DNA repair effectors were assessed by Low Density Array. The effect of RAD51 inhibitor, RI-1, was evaluated by comet and annexin V assays.

ResultsWhile all GSC lines displayed efficient DNA repair machinery following ionizing radiation, our results demonstrated heterogeneous responses within two distinct groups showing different intrinsic radioresistance, up to 4Gy for group 1 and up to 8Gy for group 2. Radioresistant cell group 2 comprising 5 out of 10 GSCs showed significantly higher RAD51 expression after IR. In these cells, inhibition of RAD51 prevented DNA repair up to 180 min after IR and induced apoptosis. In addition, RAD51 protein expression in glioblastoma seems to be associated with poor progression-free survival.

ConclusionThese results underscore the importance of RAD51 in radioresistance of GSCs. RAD51 inhibition could be a therapeutic strategy helping to treat a significant number of glioblastoma, in combination with radiotherapy.

KeywordsGlioblastoma stem cells RAD51 Radioresistance Comet assay Electronic supplementary materialThe online version of this article doi:10.1186-s12885-016-2647-9 contains supplementary material, which is available to authorized users.





Autor: Anaïs Balbous - Ulrich Cortes - Karline Guilloteau - Pierre Rivet - Baptiste Pinel - Mathilde Duchesne - Julie Godet - Odi

Fuente: https://link.springer.com/







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