Apoptosis of Hepatitis B Virus-expressing Liver Tumor Cells Induced by a High Concentration of Nucleos(t)ide Analogue

作者：Tak Eunyoung; Hwang Shin^*; Lee Han Chu; Ko Gi Young; Ahn Chul Soo; Yoon Young In; Lim Young Suk; Jun Dae Young; Kim Ki Hun; Song Gi Won; Moon Deog Bok; Ryoo Baek Yeol; Kim Nayoung; Lee Sung Gyu

来源：Anticancer Research, 2016, 36(11): 6059-6069.

DOI：10.21873/anticanres.11195

• Tenofovir
• entecavir
• covalently closed circular DNA
• HBV X protein
• transcatheter arterial chemoembolization

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.

• 出版日期2016-11