【摘要】 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。更多还原

【Abstract】 Objective To investigate the relationship between DNA-dependent protein kinase (DNA-PK) activity and anti-cancer drug sensitivity in human glioma tissues. Methods Human glioma specimens were primarily cultured and its sensitivity to several anti-cancer drugs were evaluated by MTT assay. Nuclear protein was extracted from the glioma sample of the same patient and its DNA-PK activity was determined by a biotinylated DNA-PK assay with p53-derived peptide as a specific substrate. Results DNA-PK activity varied widely among these glioma samples. Of all 36 samples, 16 showed higher DNA-PK activity (relative activity ≥0. 40) and 20 samples with lower DNA-PK activity (relative activity < 0. 40). The gliomas sensitive to DDP and VCR as evaluated by inhibition rate (IR ≥ 50% ) under plasma peak concentration (PPC) showed lower DNA-PK activity than the resistant ones (IR<50%) (t= -3.445 , P < 0.01). Furthermore, the gliomas with higher DNA-PK activity showed lower inhibition rate (IR < 50% ) than those with lower DNA-PK activity ones (t = -2. 145,P <0. 05). Conclusion DNA-PK activity is significantly associated with anti-cancer drug sensitivity to DDP and VCR in human gliomas. DNA-PK activity could be used as a new biomarker for the chemotherapy sensitivity of human gliomas.更多还原