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LipofectamineTM2000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、8Gy7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α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α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。
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.
出处
《癌症》
SCIE
CAS
CSCD
北大核心
2008年第2期139-143,共5页
Chinese Journal of Cancer
基金
国家自然科学基金(No.30070237)~~
