Combination chemotherapy of serine protease inhibitor nafamostat mesilate with oxaliplatin targeting NF-κB activation for pancreatic cancer.
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.
Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan. gocho@jikei.ac.jp
Takeshi
T
Gocho
Tadashi
T
Uwagawa
Kenei
K
Furukawa
Koichiro
K
Haruki
Yuki
Y
Fujiwara
Ryota
R
Iwase
Takeyuki
T
Misawa
Toya
T
Ohashi
Katsuhiko
K
Yanaga
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001550:Benzamidines; D045744:Cell Line, Tumor; D006146:Guanidines / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009944:Organoplatinum Compounds / Q000008:administration & dosage*; D000077150:Oxaliplatin; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010766:Phosphorylation
D001550:Benzamidines; D006146:Guanidines; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000072000:NF-KappaB Inhibitor alpha; C032855:nafamostat