title: CpG oligodeoxynucleotides enhance chemosensitivity of 5-fluorouracil in HepG2 human hepatoma cells via downregulation of the antiapoptotic factors survivin and livin.
abstract: BACKGROUND
  Recent studies indicated that a synthetic oligonucleotide containing un-methylated CpG oligodeoxynucleotides (CpG-ODN) has a potential function for cancer therapy. In this study, we evaluated the chemosensitizing effects of CpG-ODN in 5-fluorouracil (5-FU)-treated HepG2 human hepatoma cells.
  
  
  METHODS
  Cell viability assay were utilized to evaluate the direct cytotoxicity of CpG-ODN in the presence or absence of 5-FU in HepG2 cells, and apoptosis as well as cell-cycle was examined by flow cytometry analysis. The mRNA expression of Bcl-2, Livin and Survivin within HepG2 cells treated with CpG-ODN and/or 5-FU were analyzed by Real Time PCR assay in vitro.
  
  
  RESULTS
  CpG-ODN in combination with 5-FU could decrease cell viability, increase apoptosis and further induce HepG2 cells cycle arrest at S phase when compared with CpG-ODN or 5-FU. CpG-ODN or 5-FU could down-regulate the mRNA expression of Bcl-2 within HepG2 cells. The mRNA expression of Livin and Survivin decreased in cells treated with CpG-ODN alone but increased in cells treated with 5-FU alone. However, CpG-ODN in combination with 5-FU could down-regulate the mRNA expression of Livin and Survivin within HepG2 cells.
  
  
  CONCLUSIONS
  Our finding demonstrated that CpG-ODN enhanced the chemosentivity of 5-FU in HepG2 human hepatoma cells at least in part by down-regulating the expression of Livin and Survivin, leading to apoptosis and further inducing cell cycle arrest at S phase. Therefore, CpG-ODN may be a potential candidate as chemosensitizer for human hepatocellular carcinoma.
authors.forename: Sheng-Ran
authors.initials: SR
authors.lastname: Liang
authors.forename: Guang-Rui
authors.initials: GR
authors.lastname: Hu
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Fang
authors.forename: Su-Jing
authors.initials: SJ
authors.lastname: Huang
authors.forename: Jin-Song
authors.initials: JS
authors.lastname: Li
authors.forename: Ming-Yi
authors.initials: MY
authors.lastname: Zhao
authors.affiliation: School of Life Science and Biopharmaceutical, Guangdong Pharmaceutical University, Guangzhou 510006, P, R, China. mminjie@163.com.
authors.forename: Min-Jie
authors.initials: MJ
authors.lastname: Meng