Abstract
INTRODUCTION: Intra-peritoneal administration (i.p.) of paclitaxel is a useful treatment for peritoneal dissemination of malignant tumors, but the therapeutic efficacy is limited. Chemoresistance due to paclitaxel-induced nuclear factor-kappaB (NF-kappaB) activation is an important cause of suboptimal therapeutic effect. We previously reported that nafamostat mesilate (FUT175), a synthetic serine protease inhibitor, inhibits NF-kappaB activation due to suppression of IkappaBalpha phosphorylation and promotes caspase-8-mediated apoptosis in pancreatic cancer. We hypothesized that addition of FUT175 to i.p. paclitaxel may enhance anti-tumor effect in peritoneal dissemination of gastric cancer.
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