Constitutive
NF-kappaB activation plays a key role in the aggressive behavior of
pancreatic cancer. We have reported that
nafamostat mesilate, a
serine-protease inhibitor, inhibited
NF-kappaB activation and induced apoptosis in human
pancreatic cancer cells. The aim of this study is to evaluate the therapeutic efficacy of
nafamostat mesilate against
pancreatic cancer. In vitro,
nafamostat mesilate inhibited
NF-kappaB activation of human
pancreatic cancer cell line (Panc-1) by suppressing
IkappaBalpha phosphorylation and induced
caspase-8 mediated apoptosis. In vivo, Panc-1 was implanted into the back of nude mice. Five weeks after implantation,
nafamostat mesilate was injected intraperitoneally as the treatment group (n=11) three times a week for six weeks, while the control group (n=13) received vehicle only. At the end of six-week treatment, the
tumors grew up to 12.89+/-4.27 mm (mean +/- SD) in the treatment group, and 17.93+/-4.45 mm in the control group, respectively. The
tumor volume and weight of the treatment group were reduced by 43 and 61% as compared with the control group. The
tumor growth was significantly inhibited in the treatment group (p<0.0001). Assays of primary
tumors also indicated that
nafamostat mesilate inhibited
NF-kappaB activation by suppressing
IkappaBalpha phosphorylation, resulting in
caspase-8 mediated apoptosis. These results suggested that
nafamostat mesilate has anti-neoplastic property against experimental
pancreatic cancer.