不同p53功能状态的胶质瘤细胞株放射敏感性研究

Radiosensitivity of the Human Glioblastoma Cell Lines in Different p53 Function Status

目的探讨不同p53功能状态胶质瘤细胞的放射敏感性。方法采用射线照射野生型p53基因的U87和突变型P53的U251细胞株。流式细胞仪检测细胞周期和凋亡变化,成克隆实验测定细胞存活分数,采用单击多靶模型和线性二次函数模型拟合细胞存活曲线,求出放射生物学参数Do、Dq、N和α、β、SF2值。结果射线处理后U87细胞亚二倍体峰明显高于U251(P<0.05﹚,而U251细胞明显阻滞于G0/G1期;突变型p53基因的U251和野生型p53基因的U87细胞的Do值分别为1.0450、0.9652Gy;Dq值分别为1.8544、1.2524Gy;a值分别为0.13、0.525Gy-1;SF2值分别为0.722、0.241。野生型p53基因U87细胞Do、Dq和SF2值均减小,α值增大。结论野生型p53基因U87可以提高胶质瘤细胞的放射敏感性。

Objective To investigate the radiobiological characteristics of the human glioblastoma cell lines in different p53 function status. Methods Wild-type （wt）p53 U87 and mutated （mu）p53 U251 the cell lines were adopted for the study. Western blot was used to evaluate the p53 function status of the cells by p21 expression after ionizing radiation, the apotosis and cell cycle of U87 and U251 cells were analyzed by flow ey- tometry, and the clonogenic assay was performed to determine the survival fraction. The parameters Do, Dq and N for the single-hit multi-target model and the parameters et, [3 and SF2 for the linear-quadratic model were cal- culated. Results Wt p53 U87 cells had the Do of 0. 9652 Gy, the Dq ofl. 2524Gy, the ct of 0. 525 Gy-1, and the SF2 of 0.241, respectively. Mu p53 U251 cells had the Do of 1. 045 Gy, the Dq of I. 8544 Gv, the ct of 0.13 Gy- 1, and the SF2 of 0. 722, respectively. Compared with human glioblastoma U251 cells with p53 dysfunction, the decreased Do, Dq, SF2 and the increased ct were seen in wild-type p53 U87. Conclusion Wt p53 gene could enhance the radiosensitivitv of human ~lioblastoma ceil lines.