Hepatitis B virus (HBV) X protein (HBx) is thought to be involved in the development of liver cancer and alteration of cellular HBx level may influence the pathological progression of HBV-induced liver diseases. We found that the cellular levels of HBx mRNA transcript and protein in cells were greatly enhanced by adriamycin, a topoisomerase II inhibitor. Up-regulation of HBx mRNA by adriamycin was also observed in HBx transgenic mice, which was accompanied with a significant increase of VEGF mRNA, the downstream target of HBx. When we investigated the underlying mechanism, we found that half-life of HBx mRNA in HBx-expressing Chang cells was about 3 h, but was prolonged to >6 h in the presence of adriamycin. Moreover, half-life of rapidly degrading HBx protein was determined as about 15 min however, it remained almost constant until 60 min in the presence of adriamycin. These results provide the first evidence that the cellular level of HBx gene can be increased at the post-transcriptional level. (C) 2002 Elsevier Science (USA). All rights reserved.