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目的研究DNA依赖性蛋白激酶(DNA-PK)活性和脑胶质瘤化疗敏感性的关系。方法原代培养胶质瘤细胞,用MTT法检测其对6种不同抗癌药物的敏感性,以血药峰浓度(PPC)下的抑制率(IR)表示。提取同一胶质瘤组织标本中核蛋白质,用p53蛋白为特异底物的磷酸化反应检测其中的DNA-PK活性。结果不同胶质瘤组织标本中DNA-PK活性差别较大,36例组织标本中, 16例的DNA-PK活性较高(相对活性≥0．40),20例的DNA-PK活性较低(相对活性<0．40)。对 DDP、VCR敏感(IR≥50％)的肿瘤组织,DNA-PK活性低;对DDP、VCR不敏感(IR<50％)的肿瘤组织,DNA-PK活性高(t=-3．445,P<0．01)。同时,DNA-PK活性高的肿瘤组织,DDP、VCR体外抑制肿瘤细胞的IR值低;而DNA-PK活性低的肿瘤组织,相应的IR值高(t=-2．145,P<0．05)。结论胶质瘤标本的DNA-PK活性与其对DDP、VCR敏感性显著相关,DNA-PK活性的高低可能是胶质瘤化疗敏感性的一个新的标记物。
Objective To study the relationship between the DNA-dependent protein kinase (DNA-PK) activity and chemosensitivity of glioma. Methods Primary cultured glioma cells were tested for sensitivity to 6 different anticancer drugs by MTT assay and expressed as inhibition rate (IR) under peak plasma concentration (PPC). The nuclear proteins in the same glioma tissue samples were extracted, and the DNA-PK activity was detected by the phosphorylation reaction with the p53 protein as a specific substrate. Results The DNA-PK activity in different glioma tissue samples was quite different. Among the 36 samples, 16 had higher DNA-PK activity (relative activity≥0.40) and 20 patients had lower DNA-PK activity Relative activity <0.40). DNA-PK activity was low in tumor tissues sensitive to DDP and VCR (IR≥50%); DNA-PK activity was high in tumor tissues not sensitive to DDP and VCR (IR <50%) (t = -3.445, P <0.01). At the same time, the tumor cells with high DNA-PK activity, DDP and VCR had lower IR values of tumor cells in vitro. The corresponding DNA values of tumor tissues with low DNA-PK activity were higher (t = -2.145, P <0. 05). Conclusion The DNA-PK activity of glioma specimens is significantly correlated with the sensitivity of DDP and VCR. The level of DNA-PK activity may be a new marker of glioma chemosensitivity.