Presentation Study on functions of the DNA damage response factors in the cellular response to heavy ion beams

Qiang, LIU  ,  Yi, XIE  ,  Liqing, DU  ,  Yan, WANG  ,  Chang, XU  ,  Mengzheng, GUO  ,  勝部, 孝則  ,  二宮, 康晴  ,  王, 冰

A synthetic polypeptide ANTP- SmacN7 is a possible radiosensitizing agent derived from N terminal 7 amino acid sequence of Smac protein, which antagonizes a caspase inhibitor XIAP. To investigate the underlying mechanisms behind radiosensitization, we analyzed cellular responses of two non-small cell lung carcinomas (NSCLC) cell lines, H460 and A549, to low- and high-LET ionizing radiation (IR) and ANTP-smacN7. Western analysis revealed that expression of XIAP was higher in A549 than in H460. Sensitivities of these cells to iron (LET=200 kev/μm), carbon (LET=70 kev/μm) and photon (200 kvp X-rays) beams were determined by clonogenic assay. A549 cells were 1.6-2.0-fold more resistant to these IRs than H460, based on the doses required to reduce the cell survival to 50% (LD50). Flow cytometry assay.0s revealed that radio-induced cellular apoptosis emerged at 6 h and reached a peak level at 24 after IR at LD50. Notably, administration of ANTP-SmacN7 reduced the cell survival of A549 and H460 cell by 56% and 30%, respectively, after the iron irradiation at each LD50. These results suggested that ANTP-SmacN7 promotes apoptotic response to IR by antagonizing inhibitory effect of XIAP on caspase and thus being effective for cells particularly with high XIAP expression.

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