results claim that reduction of DNA PKcs can result in an improvement of TRAIL sensitivity in K562 cells, probably through modulation of DR4/DR5 and d FLIP Syk inhibition phrase. This result was followed by 2. 5 and 2. 1 fold increase of cell surface expression of DR4 and DR5, compared with those of the cells transfected with scrambled siRNA, respectively. We also examined the change of c FLIP mRNA level in K562 cells transfected with DNA PKcs siRNA, considering that the expression of c FLIP in addition to DR4/DR5 has been proven to the main determinant of TRAIL sensitivity. The mRNA level of c FLIP, particularly c FLIPS, in K562 cells was suppressed after transfection with DNA PKcs siRNA. These results suggest that the activity of DNA PK plays an essential part in the regulation of both DR4/DR5 and c FLIP expression, and considering the levels of DR4 and DR5 in K562/R3 cells with down regulated amount of DNA PKcs, factors apart from DNA PKcs may also be Gemcitabine structure involved in identifying the expression of DR4 and DR5. Next, we examined whether siRNA mediated suppression of DNA PKcs affects TRAIL induced cytotoxicity. The growth inhibitory aftereffect of TRAIL in K562 cells was significantly increased after transfection with DNA PKcs siRNA as compared with scrambled siRNA. This effect was followed by increased susceptibility to TRAIL induced apoptosis in K562 cells transfected with DNA PKcs siRNA compared with that in the cells transfected with scrambled siRNA. In order to establish the participation of DNA PKcs/Akt route in caspase dependent apoptosis induced by TRAIL, K562 cells transfected with DNA PKcs siRNA or scrambled siRNA were exposed to TRAIL. K562 cells transfected with DNAPKcs siRNA showed a low Akt phosphorylation on S473 in connection with reduced amount of DNA PKcs, although t Akt level was not improved. More over, in the current presence of TRAIL, the levels of DNA PKcs, p Akt and p Bad were remarkably decreased in K562 cells transfected with DNA PKcs siRNA. Retroperitoneal lymph node dissection Considering that the expression of c FLIP being an inhibitor of caspase was considerably reduced in DNA PKcs siRNA transfected K562 cells, we next examined whether the sensitization of TRAIL induced apoptosis by reduction of DNA PKcs was related to activation of caspase cascade. PATH induced activation of caspase, which can be situated downstream to DR4/DR5, was more enhanced in K562 cells transfected with DNA PKcs siRNA than in the cells transfected with scrambled siRNA. In addition, TRAILinduced activation of caspase 3 as well as caspase 9 was also more increased supplier Docetaxel in K562 cells transfected with DNA PKcs siRNA than in the cells transfected with scrambled siRNA. These results were followed by an increased cleavage of PARP, an substrate of caspase 3 in K562 cells transfected with DNA PKcs siRNA compared with the cells transfected with scrambled siRNA.