Nicotinamide phosphoribosyltransferase (NAMPT) is a critical rate-limiting
enzyme involved in
NAD synthesis that has been shown to contribute to the progression of
liver cancer. However, the potential role and mechanism of NAMPT in hepatitis B virus (HBV)-associated
liver cancer remain unclear. The present study assessed the expression of NAMPT in HBV-positive and -negative
liver cancer cells, and investigated whether HBV-induced NAMPT expression is dependent on
HBV X protein (HBx). In addition, the role of NAMPT in HBV replication and transcription, and in HBV-mediated
liver cancer cell growth was explored. The effects of NAMPT on the glycolytic pathway were also evaluated. Reverse transcription-quantitative PCR and western blotting results revealed that NAMPT expression levels were significantly higher in HBV-positive
liver cancer cells than in HBV-negative
liver cancer cells, and this effect was HBx-dependent. Moreover, the activation of NAMPT was demonstrated to be required for HBV replication and transcription. The NAMPT inhibitor FK866 repressed cell survival and promoted cell death in HBV-expressing
liver cancer cells, and these effects were attenuated by
nicotinamide mononucleotide. Furthermore, the inhibition of NAMPT was associated with decreased
glucose uptake, decreased
lactate production and decreased
ATP levels in HBV-expressing
liver cancer cells, indicating that NAMPT may promote the aerobic glycolysis. Collectively, these findings reveal a positive feedback loop in which HBV enhances NAMPT expression and the activation of NAMPT promotes HBV replication and HBV-mediated malignant cell growth in
liver cancer. The present study highlights the important role of NAMPT in the regulation of aerobic glycolysis in HBV-mediated
liver cancer, and suggests that NAMPT may be a promising treatment target for patients with HBV-associated
liver cancer.