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. In this experiment, to clarify the mechanism of signal transduction in the combination of TRAIL / X-irradiation-induced apoptosis in lung cancer cell line A549, the amount of apoptosis was measured by flow cytometer after the treatment of combination of X-irradiation + TRAIL, X-irradiation alone and TRAIL alone. The apoptotic cell death exposed to TRAIL + X-irradiation synergistically increased compared with that of TRAIL alone or of X-irradiation alone. In cells exposed to TRAIL alone, western blotting showed that the fragmentation of XIAP was observed and the expression of survivin and Bcl-XL significantly increased. In the case of X-irradiation alone, no fragmentation of XIAP was induced and, downregulation of survivin and upregulation of Bcl-XL occurred. In contrast, the increase in the fragmentation of XIAP and the down regulation of survivin and Bcl-XL 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 and Bcl-XL, induced by the combination treatment was responsible for synergestical enhancement of radiation-induced apoptosis in A549 cells.
