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.
Ohnishi
Ken
K
Department of Biology, Nara Medical University School of Medicine, Nara 634-8521, Japan.
Nagata
Yoko
Y
Takahashi
Akihisa
A
Taniguchi
Shigeki
S
Ohnishi
Takeo
T
D017209:Apoptosis / Q000528:radiation effects*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D005455:Fluorescent Antibody Technique; D016158:Genes, p53; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics*; D011836:Radiation Tolerance; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000037:antagonists & inhibitors* / Q000235:genetics; D014964:X-Ray Therapy
D034741:RNA, Small Interfering; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3