title: Apoptosis of Hepatitis B Virus-expressing Liver Tumor Cells Induced by a High Concentration of Nucleos(t)ide Analogue.
abstract: We investigated the expression of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) and HBV X protein (HBx) in human hepatocellular carcinoma (HCC) and evaluated the effect of high-concentration nucleos(t)ide analogs (NUCs) on liver tumor cell lines.
  
  
  
  This study consisted of three parts: part I used human blood and non-tumor liver tissues; part II used human HCC and adjacent liver tissues; and part III used an HBV-expressing liver tumor cell line.
  
  
  
  There were close correlations among blood and liver HBV DNA and liver cccDNA. HBV cccDNA and HBx were highly up-regulated in HCC compared to adjacent liver tissues despite NUC therapy. HBV cccDNA and HBx were highly up-regulated in the cccDNA-expressing HepG2.2.15 cell line. Their expression was down-regulated and apoptosis was induced by a very high concentration of NUCs in dose- and time-dependent manner.
  
  
  
  Very high concentrations of NUCs may have a novel potential to kill replicating HBV-expressing liver tumor cells.
authors: Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Eunyoung
authors: E
authors: Tak
authors: Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea shwang@amc.seoul.kr.
authors: Shin
authors: S
authors: Hwang
authors: Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Han Chu
authors: HC
authors: Lee
authors: Department of Diagnostic Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Gi-Young
authors: GY
authors: Ko
authors: Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Chul-Soo
authors: CS
authors: Ahn
authors: Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Young-In
authors: YI
authors: Yoon
authors: Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Young-Suk
authors: YS
authors: Lim
authors: Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Dae-Young
authors: DY
authors: Jun
authors: Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Ki-Hun
authors: KH
authors: Kim
authors: Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Gi-Won
authors: GW
authors: Song
authors: Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Deog-Bok
authors: DB
authors: Moon
authors: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Baek-Yeol
authors: BY
authors: Ryoo
authors: Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Nayoung
authors: N
authors: Kim
authors: Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Sung-Gyu
authors: SG
authors: Lee
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D006515:Hepatitis B virus / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000821:virology*; D009705:Nucleosides / Q000494:pharmacology*; D009711:Nucleotides / Q000494:pharmacology*
chemical_list: D009705:Nucleosides; D009711:Nucleotides
keywords: HBV X protein; Tenofovir; covalently closed circular DNA; entecavir; transcatheter arterial chemoembolization