[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).


CONCLUSIONS
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.
Shao
Cui-jie
CJ
South China State Key Laboratory for Cancer Research and Neuro-oncology Laboratory, Cancer Center, Sun Yat-sen University, Guangzhou 510060, China.
Xia
Yun-fei
YF
Shi
Hong-liu
HL
Zhang
Jun-Ying
JY
He
Yu-Xiang
YX
Chen
Zhong-ping
ZP
D000970:Antineoplastic Agents / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology*; D051747:DNA-Activated Protein Kinase / Q000378:metabolism*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005910:Glioma / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D014750:Vincristine / Q000494:pharmacology*
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D009687:Nuclear Proteins; D014750:Vincristine; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D002945:Cisplatin