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. 2008 Sep 21;14(35):5412-8.
doi: 10.3748/wjg.14.5412.

Biological impact of hepatitis B virus X-hepatitis C virus core fusion gene on human hepatocytes

Zhen Ma  1 , Qin-Hai Shen, Guo-Min Chen, Da-Zhi Zhang
Affiliations

Biological impact of hepatitis B virus X-hepatitis C virus core fusion gene on human hepatocytes

Zhen Ma et al. World J Gastroenterol. .

Abstract

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.

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Figures

Figure 1
Figure 1
PCR verifying recombinant adenoviruses of Ad-XC (A), Ad-X (B), and Ad-C (C). M: DL2000; lanes 1, 4 and 5: PAdEasy-1; lane 2: HBV X-HCV C fusion gene; lane 3: X gene; lane 6: C gene.
Figure 2
Figure 2
HepG2 cells infected with recombinant adenoviruses (× 200).
Figure 3
Figure 3
Western blotting displaying expression of fusion protein (A), HBV X protein (B), and HCV C protein (C). Lanes 1-3: Infected HepG2 cells; lane 4: Uninfected HepG2 cells.
Figure 4
Figure 4
Growth status change in HepG2 cells after infection.
Figure 5
Figure 5
Surgical specimens of tumor tissue (A) and histological examination (B) showing a 1.5 cm tumor (HE staining, × 400).
Figure 6
Figure 6
RT-PCR revealing mRNA expression of c-myc (A) and relative mRNA expression level of c-myc (B) in HepG2 cells. M: DL2000; lanes 1-5: HepG2, Ad0, Ad-C, Ad-X and Ad-XC cells (P < 0.05, Ad-XC group vs other groups).
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