胶质瘤细胞放射敏感性与ATM蛋白表达的关系

Relationship between ataxia-telangiectaxia mutated protein expression and radiosensitivity in human gliomas

目的探讨胶质瘤细胞放射敏感性与ATM蛋白表达关系。方法采用流式细胞仪检测22例原代培养胶质瘤细胞中ATM蛋白的表达，用噻唑蓝（MTT）比色法检测胶质瘤细胞以^60Co2Gy放射剂量照射后的存活分数（SF2），探讨ATM蛋白的表达量与胶质瘤放射敏感性的相关性；同时检测其中5例胶质母细胞瘤细胞及U251细胞系经^60Co照射前后ATM蛋白表达量，以了解放射对ATM蛋白表达的影响。结果原代培养的胶质瘤细胞形态多样；SF2平均值为0．417±0．176（0．162～0．735），在胶质瘤Ⅳ级与Ⅱ、Ⅲ级间差异有统计学意义（P〈0．05）；ATM蛋白表达水平随胶质瘤恶性程度的增高而增加，在高、低级别间差异有统计学意义（P〈0．05）；直线相关与回归分析显示：ATM蛋白表达水平与SF2呈显著正相关（r=0．857，P〈0．05）；5例原代培养的胶质母细胞瘤细胞及U251细胞系经照射后ATM蛋白表达水平提高。结论ATM蛋白的表达水平与胶质瘤放射敏感性密切相关，胶质瘤中存在不同放射敏感性的细胞群，放射治疗应体现个体化原则。

Objective Ataxia-telangiectaxia mutated protein （ATM） is an essential component of the signal transduction pathway that responds to DNA damage due to ionizing radiation （IR）. This study was designed to investigate the relationship between the expression of ATM and radiosensitivity in human gliomas. Methods Twenty-two specimens of primary gliomas were collected and adapted to grow in culture. The ATM expression in human gliomas was detected by flow cytometry. The intrinsic radiation sensitivity was expressed by the surviving fraction at the doses of 2 Gy （SF2）, and SF2 was determined by MTT assay. Results The mean SF2 of gliomas was 0. 417 ± 0. 176 （0. 162-0. 735 ）. The difference in SF2 between glioblastomas and gliomas with grade Ⅱ and Ⅲ was significant （ P 〈 0. 05 ）. Mean protein fluorescent intensity of ATM was variable and correlated with the malignant degree of gliomas. Regression analysis revealed a high correlation between ATM levels and SF2 in primary gliomas （r = 0. 857,P 〈 0.05 ）. In the U251 cell line and 5 cases of primary culture of glioblastomas,there was a transient increase in the expression of ATM level alter radiation, but there was no statistically significant difference （P 〉 0.05）. Conclusion The radiotherapy should present the individualized strategy. Attenuating ATM gene expression may be a successful strategy in the treatment of gliomas.