Relation between radiation sensitization and dysfunction of p53 as a transcription factor in mutated p53 cancer cells by siRNA targeting XIAP

Abstract

Radiation cancer therapy based on the predictive assay might improve the outcome of cancer therapies in patients with normal p53 function. In more advanced cancer therapy, it is crucial to develop therapeutic strategies against mutated p53 cancer cells, and thus the strategy of radiation enhancement regardless of p53 status is currently the focus of intense research. We previously demonstrated that siRNA targeting NBS1 enhanced radiation sensitivity of cancer cells p53-independently. In this report, we showed siRNA targeting XIAP (XIAP-siRNA) enhanced radiation sensitivity and radiation-induced apoptosis more effectively even in mutated p53-transfected non-small cell lung cancer cells (H1299/mp53) than in the wild-type p53-transfected cells (H1299/wtp53). Furthermore, we showed that pifithrin-α, an inhibitor of p53 activation, did not result in efficient radiation sensitization in XIAP -siRNA-treated H1299/wtp53 cells. These results suggest that dysfunction of p53 as a transcription factor is not a cause of radiation sensitization in XIAP-siRNA-treated H1299/mp53 cells.