he sensitization of TNF alpha-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in A549 by ionizing radiation in vitro

Abstract

Recently we reported additive or synergistical enhancement of X-irradiation-induced apoptosis by TRAIL (TNF-related apoptosis-inducing ligand) in solid tumor cell lines. However, the mechanism of signal transduction for apoptosis in the cell treated with the combination of TRAIL + X-irradiation is still unknown. Here, we report that the apoptotic cell death in human lung cancer cell A549 exposed to TRAIL + X-irradiation synergistically increased compared with that of TRAIL alone or of X-irradiation alone and that the fragmentation of XIAP and the downregulation of survivin was observed in the case of TRAIL alone and X-irradiation alone, respectively. Moreover, the increase in the fragmentation of XIAP and the down regulation of survivin were observed in the cells treated with the combination of TRAIL + X-irradiation. These data suggest that the strong downregulation of antiapoptotic proteins, i.e., survivin, induced by the combination treatment was responsible for synergistically enhancement of radiation-induced apoptosis in A549 cells.