Noninvasive imaging of apoptosis induced by adenovirus-mediated cancer gene therapy using a caspase-3 biosensor in living subjects.

摘要: Abstract We attempted to visualize the serial induction of caspase-3-dependent apoptosis mediated by Fas ligand/tumor necrosis factor-related apoptosis-inducing ligand (FasL/TRAIL) adenoviral gene therapy in mice bearing human glioma xenografts using a caspase-3 biosensor and monitored its therapeutic effects. Human D54 cells expressing both sensor Renilla luciferase (Rluc) were established (referred as D54-CR cells). The bioluminescence imaging (BLI) signals increased time- virus dose-dependent manner Ad-TRAIL or Ad-FasL transduction. Fluorescence-activated cell sorting (FACS) analysis revealed an increase cleaved poly(ADP-ribose) polymerase (PARP) annexin V- propidium iodide-positive depending on dosage administered virus. treatment resulted significant BLI activity tumors, which ≈ 8.2, 12.9, 46.6 times higher than those control at 12 hours, 24 96 hours posttreatment, respectively. In contrast, reduction Rluc activity, surrogate marker viability, was detected tumors treated with but not Ad-null. Overall, activation induced Ad-FasL/Ad-TRAIL successfully sensitive platform for activation.