ATM induces radioresistance of non-small cell lungcancer A549 cells by downregulation of MDMX

Background: tumor radioresistance leads to a reduction in the efficiency ofradiation therapy. it is very important to explore the cellular mechanismsleading to radioresistance and to find potential therapeutic targets, whichmight improve the efficacy of radiation therapy. this study was to investigatethe role of ataxia-telangiectasia mutated (atm) and murine double minute x(mdmx) in radioresistance in non-small cell lung cancer a549 cells and theircorresponding mechanisms of action. materials and methods: non-small celllung cancer a549 cells were irradiated with x-rays in the presence or absenceof atm inhibitor. cell survival, cell apoptosis, cell proliferation, mrna of atmand mdmx, and protein expression of atm, mdmx, γ-h2ax, caspase3, andbeclin1 were measured. results: after the inhibitor (ku60019) treatmentcombined with x irradiation, the a549 cells showed a significant decrease incolony formations compared to the group received irradiation alone. themdmx knockdown a549 cells showed a significant increase in colonyformations compared to the control group. atm downregulated theexpression of mdmx after irradiation treatment in a549 cells. irradiation ledto a significant increase in γ-h2ax expression, but mdmx knockdowndecreased the γ-h2ax expression after irradiation. the change of caspase3expression was the same as γ-h2ax. irradiation led to a significant increase ofbeclin1 expression and mdmx knockdown increased the beclin1 expressionafter irradiation. conclusion: this study indicated that atm inducedradioresistance through downregulating the expression of mdmx, which wasat least partly associated with the activation of autophagy and the decreaseof dna damage in a549 cells.