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Ku80 is highly expressed in lung adenocarcinoma and promotes cisplatin resistance

Author(s): Ma Qingshan | Li Ping | Xu Minyu | Yin Jinzhi | Su Zhenzhong | Li Wei | Zhang Jie

Journal: Journal of Experimental & Clinical Cancer Research
ISSN 1756-9966

Volume: 31;
Issue: 1;
Start page: 99;
Date: 2012;
Original page

Keywords: Ku80 | Lung cancer | Chemotherapy | siRNA | Cisplatin

Abstract Background Ku80 is crucially implicated in DNA repair, apoptosis, and chemoresistance. In this study, we aimed to assess the expression of Ku80 in clinical lung adenocarcinoma specimens, and investigate its role in the regulation of cisplatin sensitivity in cisplatin resistant human lung adenocarcinoma cells A549/DDP. Methods Tumor specimens and medical records of 106 patients with operable lung adenocarcinoma were obtained from 1998 to 2003. Ku80 mRNA and protein levels of the tumor samples, cultured human lung adenocarcinoma cells A549 cells and their cisplatin resistant variant A549/DDP cells were examined by reverse transcription PCR and western blot analysis. Ku80-specific siRNA or control scramble siRNA was transfected into A549/DDP cells, then cell sensitivity to cisplatin was examined by 3-(4,5-dimethylthia-zol-2-yl)-2,5-diphenyltetrazolium bromide assay and apoptosis was assessed by flow cytometric analysis. In addition, the levels of cleaved caspase-3 and cleaved PARP in the treated cells were detected by western blot analysis. Results Total 83.3% (20/24) cisplatin-resistant tumors had high Ku80 expression, while 8.3% (4/48) cisplatin-sensitive tumors had high Ku80 expression (p 
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