Enhanced radiation-mediated cell killing of human cervical cancer cells by small interference RNA silencing of ataxia telangiectasia-mutated protein.

The ataxia telangiectasia-mutated (ATM) protein, which is mutated in the inherited disease ataxia telangiectasia (AT), is a key activator of cell cycle checkpoint, initiating cell response to DNA damage and ensuring genomic stability. AT cells exhibit defects in all cellular responses to ionizing radiation and radiomimetic chemicals. Inactivation of ATM may therefore make cells fail to execute many responses to DNA damage and improve the cells' sensitivity to radiation. Recent developments in the use of small interference RNA molecules (siRNAs) to inhibit specific protein expression have highlighted the potential use of siRNA as a therapeutic agent. In this study, we have designed and exogenously delivered plasmids encoding siRNAs targeting ATM to human cervical carcinoma SiHa cells and generated a stable cell line, SiHa(ATM). SiHa(ATM) cells displayed minimal levels of ATM protein and showed a marked increase in sensitivity to radiation. Together, these data provide strong evidence for the potential use of siRNA as a novel radiation/chemotherapy-sensitizing agent.