Open Access

Anti-tumor effect by inhibition of NF-κB activation using nafamostat mesilate for pancreatic cancer in a mouse model

  • Authors:
    • Kenei Furukawa
    • Tomonori Iida
    • Hiroaki Shiba
    • Yuki Fujiwara
    • Tadashi Uwagawa
    • Yohta Shimada
    • Takeyuki Misawa
    • Toya Ohashi
    • Katsuhiko Yanaga
  • View Affiliations

  • Published online on: October 1, 2010     https://doi.org/10.3892/or_00000928
  • Pages:843-850
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Abstract

Constitutive NF-κB activation plays a key role in the aggressive behavior of pancreatic cancer. We have reported that nafamostat mesilate, a serine-protease inhibitor, inhibited NF-κB 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-κB activation of human pancreatic cancer cell line (Panc-1) by suppressing IκBα 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-κB activation by suppressing IκBα phosphorylation, resulting in caspase-8 mediated apoptosis. These results suggested that nafamostat mesilate has anti-neoplastic property against experimental pancreatic cancer.

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October 2010
Volume 24 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

2016 Impact Factor: 2.662
Ranked #31/217 Oncology
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APA
Furukawa, K., Iida, T., Shiba, H., Fujiwara, Y., Uwagawa, T., Shimada, Y. ... Yanaga, K. (2010). Anti-tumor effect by inhibition of NF-κB activation using nafamostat mesilate for pancreatic cancer in a mouse model . Oncology Reports, 24, 843-850. https://doi.org/10.3892/or_00000928
MLA
Furukawa, K., Iida, T., Shiba, H., Fujiwara, Y., Uwagawa, T., Shimada, Y., Misawa, T., Ohashi, T., Yanaga, K."Anti-tumor effect by inhibition of NF-κB activation using nafamostat mesilate for pancreatic cancer in a mouse model ". Oncology Reports 24.4 (2010): 843-850.
Chicago
Furukawa, K., Iida, T., Shiba, H., Fujiwara, Y., Uwagawa, T., Shimada, Y., Misawa, T., Ohashi, T., Yanaga, K."Anti-tumor effect by inhibition of NF-κB activation using nafamostat mesilate for pancreatic cancer in a mouse model ". Oncology Reports 24, no. 4 (2010): 843-850. https://doi.org/10.3892/or_00000928