The
hepatitis B virus X protein (HBx) plays an important role in the development of
hepatocellular carcinoma (HCC). The relationship was examined between HBV
antigens and IAP (inhibitor of apoptosis) family in development of HCC. The expression levels of HBV
antigens (
HBsAg,
HBcAg, and HBxAg) and members of the IAP family (
survivin, XIAP, cIAP-1, and cIAP-2) were detected immunohistochemically in tissues from 34 cases of HCC and 30 cases of
liver cirrhosis. The positive rate of
survivin was higher than these three molecules in all three tissue types (P < 0.05). The positive rates of HBxAg and
survivin were high in HCC (76.5% and 88.2%), paratumor (85.3% and 91.2%), and
liver cirrhosis (100% and 93.3%) tissues, with no significant differences between the
survivin- and HBxAg-positive rates (each P > 0.05). To examine the effect of HBx on
survivin expression, plasmid pCMV-X (encoding the HBx gene) was transfected transiently with or without plasmid pcDNA3-sur (encoding the
survivin gene) into H7402
hepatoma cells and L-O2 human normal liver cells. Cells over-expressing HBx alone showed increased apoptosis along with a dose-dependent increase in
survivin levels. However, co-expression of
survivin inhibited the HBx-induced apoptosis. To examine the effect of HBx on
survivin in
hepatoma cells without apoptosis, plasmid pCMV-X was transfected stably into human
hepatoma H7402 cells and L-O2 cells. These H7402-X and L-O2-X cells showed high-level expression of both HBx and
survivin, but did not show apoptosis. The addition of pSilencer 3.0-X, an RNAi vector targeting the HBx gene, reduced the expression levels of
survivin protein in H7402-X cells. Collectively, these data demonstrate that HBx upregulates
survivin expression in
hepatoma tissues, suggesting that HBx and
survivin may both be involved in
carcinogenesis of HCC.