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.


CONCLUSIONS
Pretreatment determination of DNA-PK/Ku86 activities might be helpful in identifying patients who will actually benefit from platinum-based treatment.
Shao
Cui-Jie
CJ
State Key Laboratory for Cancer Research in Southern China, Department of Neurosurgery/Neuro-oncology, Cancer Center, Sun Yat-Sen University Guangzhou, Guangdong, P.R. China.
Fu
Jun
J
Shi
Hong-Liu
HL
Mu
Yong-Gao
YG
Chen
Zhong-Ping
ZP
D000328:Adult; D034961:Antigens, Nuclear / Q000187:drug effects / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001681:Biological Assay; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use; D051747:DNA-Activated Protein Kinase / Q000187:drug effects / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D005260:Female; D005910:Glioma / Q000188:drug therapy / Q000201:enzymology*; D006801:Humans; D000072200:Ku Autoantigen; D008297:Male; D008875:Middle Aged; D013778:Tetrazolium Salts; D013844:Thiazoles; D014407:Tumor Cells, Cultured
D034961:Antigens, Nuclear; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D013778:Tetrazolium Salts; D013844:Thiazoles; D051747:DNA-Activated Protein Kinase; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen; C022616:thiazolyl blue; D002945:Cisplatin