Abrogation of the p38 MAPKα signaling pathway does not promote radioresistance but its activity is required for 5-Fluorouracil-associated radiosensitivity
Menée sur des lignées cellulaires dérivées de divers types tumoraux (côlon-rectum, poumon, rein, glioblastome), cette étude montre que la suppression de la voie de signalisation p38MAPKα ne confère pas de radiorésistance aux cellules tumorales mais que cette signalisation est nécessaire pour l'utilisation du 5-fluorouracile comme radiosensibilisant
The p38 Mitogen Activated Protein Kinase (MAPK) signaling pathway has become a major player in the response to DNA-damage. A growing body of evidences has been relating this signaling pathway to the cellular response to ionizing radiation (IR), suggesting a role in radioresistance. Here, we study the implication of this signaling pathway in the response to IR in terms of radioresistance. To this end we used 10 different cell lines derived from several types of tumours (colorectal, non-small cell lung cancer -NSCLC-, renal and glioblastoma). Although p38 MAPK is transiently activated by IR, our data, obtained by genetic and chemical approaches, showed that this signaling pathway is not implicated in cellular viability after IR exposure. Indeed, down-modulation of this signaling pathway promotes a mild radiosensitivity depending on the cell line. However, it is remarkable that lack of p38 MAPK α abrogates the radiosensitizing effect of 5-Fluorouracil (5-FU) in HCT116 cell line, supporting the role of this MAPK in the radiosensitizing action of 5-FU.
http://www.sciencedirect.com/science/article/pii/S0304383513000967