DR4 and DR5 were caused somewhat in K562/R3 VEGFR inhibition cell, although not in K562 cells after treatment with TRAIL. The increased sensitivity might be determined by these changes in TRAIL receptors to TRAIL in K562/R3 cells. Since DR4 and DR5 were caused after transfection with DNA PKcs siRNA, some factors apart from DNA PKcs also might be involved in the dedication of sensitivity and the expression regulation of TRAIL receptors to TRAIL in K562/R3 Docetaxel Taxotere cells. To know the function of DNA PKcs in TRAIL resistance, we silenced DNA PKcs in K562 cells applying small interfering RNA. The targeted inhibition of DNA PKcs generated up regulation of DR4/DR5 and concurrent down regulation of both c FLIPL and cFLIPS, especially c FLIPS. The endogenous expression of c FLIP,which has a sequence homology with caspase and 10 but no protease activity, inhibits apoptosis by preventing the processing of caspase. Ahighlevel of c FLIP is correlatedwithTRAIL opposition in some tumor types, and hence down regulation of c FLIP has been implicated in enhancement of TRAIL induced apoptosis. Additionally, the level of p Akt was also decreased by transfectionwithDNA PKcs siRNA,which is similar to K562/R3 Cellular differentiation cells with lowlevels of DNA PKcs and p Akt. It’s demonstrated an ability that the introduction of a negative Akt adenoviral develop constantly reduced FLIP expression, and the decline of Akt exercise by LY294002 reduced the expression of FLIPS and the overexpression of constitutively active Akt in the TRAIL sensitive and painful cell line, SNU 66, rendered the cell line resistant to TRAIL. For that reason, DNA PK action did actually influence the appearance of DR4, DR5 and h FLIP via p Akt. Recently, mTORC2 was proved to be the elusive PDK2 responsible for phosphorylating Akt on S473, which can be also regarded as phosphorylated by DNA PKcs. In K562 cells, however, the order Crizotinib phosphorylated position of Akt Ser473 was well correlated with the experience of DNA PKcs and could be suppressed almost completely by mix of DNAPKcs siRNA and TRAIL. Consequently, DNA PK, perhaps not mTORC2, might be a key determinant for Akt S473 phosphorylation in K562 cells. The regulation of TRAIL receptors and concurrent downregulation of c FLIP induced by inhibition of DNA PKcs was followed by increased sensitivity to TRAIL induced apoptosis with increased activation of caspase, 9 and three, which play a critical position in TRAIL induced apoptosis. Thus, the specific inhibition of DNA PKcs would sensitize K562 cells to TRAIL induced apoptosis via inactivation of DNA PKcs/Akt pathway and subsequent increase of TRAIL receptor mediated apoptotic pathway.