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。
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.
出处
《中华肿瘤杂志》
CAS
CSCD
北大核心
2006年第5期342-344,共3页
Chinese Journal of Oncology
基金
国家自然科学基金资助项目(30271329)
