BACKGROUND/AIMS: Des-gamma-carboxy prothrombin (DCP), an aberrant prothrombin 
produced by hepatocellular carcinoma (HCC) cells, is known as a marker for HCC. 
Recent studies indicated that high levels of DCP are associated with the 
malignant potential of HCC. In this study, we aimed to investigate the 
association of DCP with gefitinib treatment failure in HCC and whether DCP 
counteracts gefitinib-induced growth inhibition and apoptosis of HCC.
METHODS: The experiments were performed in HCC cell lines HepG2 and PLC/PRF/5. 
The effects of gefitinib on HCC in the presence or absence of DCP were evaluated 
by the 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl-tetrazolium bromide (MTT) 
assay. Apoptotic cells were identified by Annexin V-FITC/PI staining. Western 
blotting was performed to analyze the expressions of molecules related to the 
apoptotic caspase-dependent pathway and epidermal growth factor receptor (EGFR) 
pathway.
RESULTS: Gefitinib inhibited HCC cell proliferation and induced apoptosis in HCC 
cells. The effects of gefitinib on HCC cells were antagonized by DCP. In the 
presence of DCP, HCC cells were resistant to the gefitinib-induced inhibition of 
proliferation and stimulation of apoptosis. DCP prevented the activation of the 
apoptotic caspase-dependent pathway induced by gefitinib. These antagonistic 
effects of DCP also arose from its ability to up-regulate EGFR, c-Met and 
hepatocyte growth factor (HGF) in HCC cells.
CONCLUSION: DCP antagonized gefitinib-induced HCC cell growth inhibition by 
counteracting apoptosis and up-regulating the EGFR pathway. High levels of DCP 
might thus lead to low response rates or possibly no response to gefitinib in 
patients with HCC.