The relationship between the down-regulation of DNA-PKcs or Ku70 and the chemosensitization in human cervical carcinoma cell line HeLa.
The aim of this study was to clarify the function of non-homologous end-joining (NHEJ) in tumorigenesis and chemoresistance, and to explore the potential of DNA-PK as a target of reversal of chemoresistance and enhancing the sensitivity of cells to chemotherapeutic agents. Plasmid vectors pSIREN-Ku70shRNA and pSIREN-DNA-PKcssh-RNA, which coded small interfering RNA of Ku70 and DNA-PKcs, were constructed and transfected into human cervical cancer cell line HeLa. The relationship between the down-regulation of Ku70 or DNA-PKcs and tumor cell proliferation and the sensitivity of cells to chemotherapeutic agents were analyzed. Down-regulation of Ku70 and DNA-PKcs expression inhibited cell proliferation, and increased cell apoptosis in DDP-treated HeLa cells. DNA-PK might play an important role in drug resistance, and inhibition of the DNA-PK expression suppressed the growth of tumor cells and enhanced the sensitivity of cells to chemotherapeutic agents.
Tian
Xiaoyu
X
Cancer Biology Research Center, Tongji Hospital, Tongji Medical School, Huazhong University of Science and Technology, Hubei 430030, P.R. China.
Chen
Gang
G
Xing
Hui
H
Weng
Danhui
D
Guo
Yunhong
Y
Ma
Ding
D
D034961:Antigens, Nuclear / Q000235:genetics / Q000378:metabolism*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D015153:Blotting, Western; D049109:Cell Proliferation; D002945:Cisplatin / Q000008:administration & dosage; D051747:DNA-Activated Protein Kinase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000008:administration & dosage; D020868:Gene Silencing / Q000502:physiology; D006367:HeLa Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D000072200:Ku Autoantigen; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019772:Topotecan / Q000008:administration & dosage