Combination chemotherapy of serine protease inhibitor nafamostat mesilate with oxaliplatin targeting NF-κB activation for pancreatic cancer

Cancer Lett. 2013 Jun 1;333(1):89-95. doi: 10.1016/j.canlet.2013.01.019. Epub 2013 Jan 21.


In this study, we assessed if nafamostat mesilate may enhance anti-tumor effects of oxaliplatin on Panc-1 cells and pancreatic cancer mouse model. In combination treatment with nafamostat mesilate and oxaliplatin, NF-κB activation was inhibited by suppressing IκBα phosphorylation, and caspase-8-mediated apoptosis was more prominent than that treated with oxaliplatin alone, both in vitro and in vivo. Nafamostat mesilate reduced proliferation rate of Panc-1 cells as compared with oxaliplatin alone in vitro and enhanced oxaliplatin-induced tumor growth inhibition in vivo. Combination chemotherapy using nafamostat mesilate and oxaliplatin induces synergistic cytotoxicity in pancreatic cancer and could be a novel strategy for treatment.

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Apoptosis / drug effects
  • Benzamidines
  • Cell Line, Tumor
  • Guanidines / administration & dosage*
  • Guanidines / pharmacology
  • Humans
  • I-kappa B Proteins / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / antagonists & inhibitors*
  • Organoplatinum Compounds / administration & dosage*
  • Oxaliplatin
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / pathology
  • Phosphorylation


  • Benzamidines
  • Guanidines
  • I-kappa B Proteins
  • NF-kappa B
  • NFKBIA protein, human
  • Nfkbia protein, mouse
  • Organoplatinum Compounds
  • Oxaliplatin
  • NF-KappaB Inhibitor alpha
  • nafamostat