[Effect of DNA-PKcs antisense oligodeoxynucleotides on radiosensitivity of nasopharyngeal carcinoma cell lines with different p53 function statuses].

ABSTRACT

BACKGROUND & OBJECTIVE: DNA-dependent protein kinase (DNA-PK) can repair DNA double-strand break. This study was to observe the effect of DNA-PKcs antisense oligodeoxynucleotides (ASODN) on the radiosensitivity of nasopharyngeal carcinoma (NPC) cell lines with normal or abnormal p53 functions. METHODS: DNA-PKcs ASODN was transfected into CNE-1 and CNE-1-wtp53 cells. These cells were irradiated with 0, 0.5, 1, 2, 4, 6, or 8 Gy X-ray. Cell survival was determined by clonogenic assay. The parameters D0, Dq, and N for the single-hit multitarget model and the parameters alpha, beta, alpha/beta, and SF2 for the linear-quadratic model were calculated to evaluate the changes of radiosensitivity. RESULTS: The alpha values before DNA-PKcs ASODN transfection were 0.03 in CNE-1 cells and 0.05 in CNE-1-wtp53 cells; the alpha values after transfection were 0.04 in CNE-1 cells and 0.27 in CNE-1-wtp53 cells. The SF2 before transfection were 0.73 in CNE-1 cells and 0.50 in CNE-1-wtp53 cells; the SF2 after transfection were 0.45 in CNE-1 cells and 0.21 in CNE-1-wtp53 cells. The D0 before transfection were 2.08 Gy in CNE-1 cells and 1.13 Gy in CNE-1-wtp53 cells; the D0 after transfection were 1.07 Gy in CNE-1 cells and 0.83 Gy in CNE-1-wtp53 cells. The Dq before transfection were 2.04 Gy in CNE-1 cells and 1.36 Gy in CNE-1-wtp53 cells; the Dq after transfection were 1.24 Gy in CNE-1 cells and 0.73 Gy in CNE-1-wtp53 cells. The parameter alpha of CNE-1 cells was increased after DNA-PKcs ASODN transfection, but the parameters SF2, D0, and Dq were decreased after transfection. CONCLUSION: DNA-PKcs ASODN could enhance the radiosensitivity of CNE-1 cells regardless of p53 function status.