胶质瘤DNA依赖性蛋白激酶活性与化疗药物敏感性的关系

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。

Correlation of DNA-PK activity with anti-cancer drug-sensitivity in human gliomas

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 > or = 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 > or = 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.