Noninvasive bioluminescent and microPET imaging for the regulation of NF-kappaB in human hepatoma-bearing mice.

摘要

The activity of nuclear factor-kappaB (NF-kappaB), a nuclear transcription factor, influences both critical tumor promotion and host-tumor interactions. Preventing NF-kappaB activation may thus inhibit the development of cancer. Therefore, development of easy and rapid methods to evaluate the regulation of NF-kappaB is needed for drug discovery. The aim of this study was to visualize the regulation of NF-kappaB by real-time, noninvasive bioluminescence and microPET imaging in vivo. MATERIALS AND METHODS: A highly responsive HepG2/NF-kappaB/luc clone L for 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced tumor promotion inhibited by methotrexate (MTX) was selected by high-throughput bioluminescent imaging (BLI) in vitro. BLI and microPET using (18)F-fluorodeoxyglucose (FDG) imaging were performed in HepG2/NF-kappaB/Luc/L hepatoma-bearing SCID mice. RESULTS: The luciferase expression by BLI assay reflected that the TPA-induced NF-kappaB activity was suppressed by MTX after 16 h treatment. A positive correlation between in vitro and in vivo MTX-suppressed TPA-induced NF-kappaB activity was indicated. MicroPET imaging could not demonstrate any decrease in FDG uptake during the early stage at 24 h after TPA and MTX treatment. CONCLUSION: BLI directly revealed that MTX inhibited cellular transformation by suppressing NF-kappaB activity. Molecular imaging would accelerate the validation of the gene regulation of tumor cells in preclinical cellular and mouse models.