Abstract:Objective To investigate the relationship of hepatitis B virux x gene (HBx) and vascular endothelial growth factor receptor 3 (VEGFR3) gene with hepatitis B-related liver cancer and the effects of aqueous extract of Phyllanthus urinaria L. (AEP) on the expression of HBx and VEGFR3. Methods Sixty Balb/c nude mice were randomly assigned to ten groups. A subcutaneous xenograft tumor model was induced by transplanting these nude mice with HepG2-HBx cells, HepG2-chloramphenicol acetyltransferase (CAT) cells, or HepG2-VEGFR3 cells. The treated mice were given AEP, normal saline (NS), or cyclophosphamide (CTX) for six weeks. The growth of xenograft tumor was evaluated at different time points after the model was induced. Serum alpha-fetoprotein (AFP) levels were determined by enzyme-linked immunosorbent assay. The protein expression of HBx and VEGFR3 in xenograft tumor was measured by Western blot. Results The hepatoma xenograft model was successfully induced in nude mice. Each group showed a significant increase in body weight over time. At the end of the experiment, among all mice transplanted with HepG2-HBx cells, the AEP group had a significantly lower tumor weight than the CTX group (P<0.05), and it had a significantly higher AFP level (P<0.05) and a significantly lower expressionof HBx in xenograft tumor (P<0.05), as compared with the NS group. Among the mice transplanted with the same HepG2 cells, the AEP group had the lowest expression of VEGFR3, but there was no significant difference in VEGFR3 expression between the AEP group and CTX group (P>0.05); the AEP group and CTX group had significantly lower VEGFR-3 expression levels than the NS group (P<0.05). Among the mice receiving the same intervention, those transplanted with HepG2-HBx cells and HepG2-CAT cells had significantly lower expression of VEGFR3 in xenograft tumor than those transplanted with HepG2-VEGFR3 cells (P<0.01). Conclusion AEP can directly suppress the protein expression of HBx and VEGFR3 in tumor tissues or indirectly suppress the protein expression of VEGFR3 by suppressing HBx expression, thus inhibiting the growth of hepatoma xenograft.