Basic Research
Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Sep 21, 2008; 14(35): 5412-5418
Published online Sep 21, 2008. doi: 10.3748/wjg.14.5412
Biological impact of hepatitis B virus X-hepatitis C virus core fusion gene on human hepatocytes
Zhen Ma, Qin-Hai Shen, Guo-Min Chen, Da-Zhi Zhang
Qin-Hai Shen, Guo-Min Chen, Da-Zhi Zhang, Ma Zhen, Institute for Viral Hepatitis, Chongqing Medical University, Chongqing 400010, China
Author contributions: Chen GM, Ma Z designed the research; Shen QH, Ma Z performed the research; Shen QH, Zhang DZ and Ma Z analyzed the data; Ma Z wrote the paper.
Correspondence to: Guo-Min Chen, Institute for Viral Hepatitis, Chongqing Medical University, Chongqing 400010, China.
Telephone: +86-23-63712639 Fax: +86-23-63712639
Received: May 9, 2006
Revised: May 25, 2008
Accepted: June 1, 2008
Published online: September 21, 2008

AIM: To investigate the biological impact of hepatitis B virus X- hepatitis C virus core (HBV X-HCV C) fusion gene on hepatoma cells.

METHODS: The recombinant adenoviruses Ad-XC, Ad-X and Ad-C expressing HBV X-HCV C fusion gene, HBV X gene and HCV C gene were constructed, respectively. Hepatoma cells were infected with different recombinant adenoviruses. MTT, colony-forming experiment, FCM, TUNEL assay were performed to observe the biological impact of the HBV X-HCV C fusion gene on liver cells.

RESULTS: MTT showed that the Ad-XC group cells grew faster than the other group cells. Colony-forming experiment showed that the colony-forming rate for the Ad-XC group cells was significantly higher than that for the other group cells. FCM analysis showed that Ad-XC/Ad-X/Ad-C infection enhanced the progression of G1→S phase in the HepG2 cell cycle. The apoptosis index of the Ad-XC, Ad-X, Ad-C group cells was significantly lower than that of the Ad0 and control group cells. Semi-quantitative RT-PCR showed that the expression level of c-myc was the highest in Ad-XC infected cells. Tumor formation was found at the injected site of mice inoculated with Ad-XC-infected LO2 cells, but not in control mice.

CONCLUSION: Ad-XC, Ad-X and Ad-C facilitate the proliferation activity of HepG2 cells and inhibit their apoptosis in vitro. The effect of Ad-XC is significantly stronger than that of Ad-X and Ad-C. Up-regulation of c-myc may be one of the mechanisms underlying the synergism of HBV X and HCV C genes on hepatocarcinogenesis in athymic nude mice.

Keywords: Hepatitis B virus X gene, Hepatitis C virus core gene, Hepatocellular carcinoma, Proliferation, Apoptosis