Effective enhancement of X-ray-induced apoptosis in human cancer cells with mutated p53 by siRNA targeting XIAP.

The X-chromosome-linked inhibitor of the apoptosis protein (XIAP) is known to be an inhibitory factor for caspase-3. The aim of our study was to see whether radiation-induced apoptosis is enhanced by RNA interference targeting the XIAP through an elevation of caspase-3 activity, and whether the effect of XIAP depression depends on the p53 status of cancer cells. Two types of transformed human cultured non-small cell lung cancer cells (H1299) were used: wild-type p53-transfected cells (H1299/wtp53) and mutated p53-transfected cells (H1299/mp53). When 21-mer siRNA targeting XIAP (XIAP-siRNA) was transfected into these cells using liposomes, a suppression of the constitutive XIAP protein expression was observed. XIAP-siRNA enhanced radiation sensitivity in H1299/wtp53 and in H1299/mp53 cells and was very effective in H1299/mp53 cells. Radiation-induced apoptosis and the activation of caspase-3 were more elevated by XIAP-siRNA in the H1299/mp53 cells than in H1299/ wtp53. These results suggest that XIAP-siRNA is a possible candidate for a radiation sensitizer in cancer radiotherapy, especially in cells with mutated p53.