Abstract: Objective To investigate the effect of c-Met inhibitor cabozantinib (XL-184) in inhibiting Listeria monocytogenes (LM)
from invading Caco-2 cells to reduce the cell injury. Methods The cell invasion capacity of LM was assayed in Caco-2 cells
incubated with different doses of XL-184 for different durations. Caco-2 cells incubated with XL-184 were seeded on the upper
room of the transwell chamber, and the cell monolayer was exposed to LM infection followed by addition of horseradish
peroxidase (HRP). The trans-epithelial electric resistance (TEER), HRP concentration and LM colony-forming unit (CFU) were
measured in the cell monolayer. Fluorescent staining was used to evaluate the cell viability, and LDH release from the cells was
examined to assess the changes in cell membrane permeability. Results XL-184 significantly decreased LM invasion rate in
Caco-2 cells in a dose- and time-dependent manner (P=0.000), and this effect was enhanced by co-incubation of the cells with
ampicillin (P<0.05). In the cell membrane permeability assay in the monolayer cells, XL-184 markedly inhibited LM-induced
reduction of TEER (P<0.05) and significantly suppressed LM-induced enhancement of cell membrane permeability shown by
reduced HRP concentration and LM count in the lower chamber (P=0.000). The cells infected with LM showed significantly
lowered cell viability, which was rescued by XL-184 (P<0.01); XL-184 also dose-dependently reduced LDH release from the
cells (P<0.05). Conclusion XL-184 can suppress LM invasion in Caco-2 cells to reduce the cell injury, suggesting its value as a
promising candidate agent for prevention and treatment of LM infections.