The aim of this study was to clarify the function of non-homologous end-joining (NHEJ) in tumorigenesis and chemoresistance, and to explore the potential of DNA-PK as a target of reversal of chemoresistance and enhancing the sensitivity of cells to chemotherapeutic agents. Plasmid vectors pSIREN-Ku70shRNA and pSIREN-DNA-PKcssh-RNA, which coded small interfering RNA of Ku70 and DNA-PKcs, were constructed and transfected into human cervical cancer cell line HeLa. The relationship between the down-regulation of Ku70 or DNA-PKcs and tumor cell proliferation and the sensitivity of cells to chemotherapeutic agents were analyzed. Down-regulation of Ku70 and DNA-PKcs expression inhibited cell proliferation, and increased cell apoptosis in DDP-treated HeLa cells. DNA-PK might play an important role in drug resistance, and inhibition of the DNA-PK expression suppressed the growth of tumor cells and enhanced the sensitivity of cells to chemotherapeutic agents.

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