中文摘要：

背景与目的：DNA依赖性蛋白激酶（DNA-dependent protein kinase，DNA-PK）是一种双链断裂修复蛋白，可以修复细胞的DNA双链断裂损伤。本研究通过转染DNA-PKcs反义寡核苷酸入鼻咽癌细胞株，探讨DNA-PKcs反义寡核苷酸对不同p53功能状态的鼻咽癌细胞株的放射敏感性的影响。方法：利用Lipofectamine^TM 2000转染DNA-PKcs反义寡核苷酸入鼻咽癌细胞株CNE-1和CNE-1-wtp53；设0、0．5、1、2、4、6、8 Gy 7个放射剂量点，用集落形成法分析转染反义寡核苷酸前后细胞的存活情况，并分别用线性二次模型和单击多靶模型拟合出细胞的剂量存活曲线，求出放射生物学参数α、β、α／β、SF2、D0、Dq和N值，评价细胞放射敏感性的变化。结果：转染DNA-PKcs反义寡核苷酸前，CNE-1和CNE-1-wtp53的仅值分别为0．03、0．05，SF2值分别为0．73、0．50，D0值分别为2．08Gy、1．13Gy，Dq值分别为2．04Gy、1．36Gy。转染DNA-PKcs反义寡核苷酸后，CNE-1和CNE-1-wtp53的仅值分别为0．04、0．26，SF2值分别为0．45、0．21，D0值分别为1．07Gy、0．83Gy，Dq值分别为1．24Gy、0．73Gy。转染DNA—PKcs反义寡核苷酸后，鼻咽癌细胞的α值增大，SF2、D0、Dq值均减小。结论：DNA—PKcs反义寡核苷酸可逆转CNE—1的辐射抗性，该逆转作用不依赖细胞的p53功能状态。

英文摘要：

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 α, β, α/β, and SF2 for the linear-quadratic model were calculated to evaluate the changes of radiosensitivity, RESULTS： The α values before DNA-PKcs ASODN transfection were 0.03 in CNE-1 cells and 0.05 in CNE-1-wtp53 cells; the α 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 α 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.