Activities of DNA-PK and Ku86, but not Ku70, may predict sensitivity to cisplatin in human gliomas.

OBJECTIVE

This study was designed to investigate the relationship between activities of DNA-dependent protein kinase (DNA-PK), its subunits Ku86/Ku70, and sensitivities to cisplatin in human glioma samples.

METHODS

Thirty-six glioma samples from patients without prior treatment before neurosurgery were included in this study. The sensitivities to cisplatin as indicated by IC(50) (the inhibitory concentration leading to 50% cell death) were assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenytetrazolium (MTT) assay; activities of DNA-PK and Ku70/Ku86 were analyzed by SigmaTECT DNA-Dependent Protein Kinase Assay System and Ku70/Ku86 DNA Repair Kit, respectively.

RESULTS

Sensitivities to cisplatin correlated with the activities of DNA-PK/Ku86, but not with the Ku70 or other clinical parameters such as age, sex of the patients, pathological gradings of the tumors, or tumor size. The levels of DNA-PK activities also associated with pathological grading and Ku86, but not with other clinical parameters. The tumors of the patients who failed to respond to cisplatin-based chemotherapy tended to display higher activity levels of DNA-PK and Ku86. Furthermore, platinum-based chemotherapy did not result in significant changes of DNA-PK/Ku activities in four matched samples before and after chemotherapy.

CONCLUSION

Pretreatment determination of DNA-PK/Ku86 activities might be helpful in identifying patients who will actually benefit from platinum-based treatment.