Inhibition of Nuclear Factor-κB Enhances the Antitumor Effect of Paclitaxel Against Gastric Cancer with Peritoneal Dissemination in Mice

摘要: Intraperitoneal (i.p.) administration of paclitaxel is useful for treating malignant tumors with peritoneal dissemination, but the therapeutic efficacy limited. Chemoresistance due to paclitaxel-induced nuclear factor-kappa B (NF-κB) activation an important cause suboptimal efficacy. The purpose this study was prove that addition nafamostat mesilate (FUT-175), a synthetic serine protease inhibitor and NF-κB inhibitor, i.p. enhances antitumor effects against gastric cancer dissemination. In vitro, we assessed activity apoptosis in response treatment FUT-175 alone, or combination human cell line (MKN-45). vivo, established dissemination nude mice by injection MKN-45 cells. animals received injections alone three times week (FUT-175 group), once (paclitaxel (combination group) week, respectively. group, inhibited enhanced comparison those other groups both vitro vivo. number weight nodules were significantly lower than group (p = 0.0009 p = 0.0417, respectively). survival analysis, had better (p = 0.0048). effect inhibiting mice.