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 ≥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 (IR50%) (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.