Eunyoung Tak1, Shin Hwang2, Han Chu Lee3, Gi-Young Ko4, Chul-Soo Ahn5, Young-In Yoon5, Young-Suk Lim3, Dae-Young Jun1, Ki-Hun Kim5, Gi-Won Song5, Deog-Bok Moon5, Baek-Yeol Ryoo6, Nayoung Kim1, Sung-Gyu Lee5. 1. Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. 2. Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea shwang@amc.seoul.kr. 3. Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. 4. Department of Diagnostic Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. 5. Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. 6. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Abstract
BACKGROUND/AIM: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: Very high concentrations of NUCs may have a novel potential to kill replicating HBV-expressing liver tumor cells. Copyright
BACKGROUND/AIM: We investigated the expression of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) and HBV X protein (HBx) in humanhepatocellular carcinoma (HCC) and evaluated the effect of high-concentration nucleos(t)ide analogs (NUCs) on liver tumor cell lines. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: Very high concentrations of NUCs may have a novel potential to kill replicating HBV-expressing liver tumor cells. Copyright