Table 2.
All studies mentioned above that have considered nafamostat mesylate.
| Author, reference, year | Drug/s | Tumor target | Molecular mechanisms of action | Results |
|---|---|---|---|---|
| Jikuhara et al. [49] 2003 | nafamostat mesylate | human colon cancer cell line (DLD-1) | (1) inhibition of PAR-2 stimulation via MAPK- and COX-dependent manner (2) inhibition of VEGF and FGF-2 levels |
inhibition of tumor cell growth, angiogenesis, invasion, metastasis |
|
| ||||
| Yoshii et al. [50] 2005 | nafamostat mesylate | human colon cancer cell line (DLD-1) | (1) Inhibition of PAR-2 stimulation via MAPK- and COX-dependent manner (2) Inhibition of the release of IL-6 and GM-CSF |
inhibition of angiogenesis, cell growth, invasion, metastasis |
|
| ||||
| Tajima et al. [51] 2001 | nafamostat mesylate | several human pancreatic cancer cell lines | antagonizing TAT-induced activation of PAR-2 | inhibition of tumor cell growth and invasion |
|
| ||||
| Ohta et al. [52] 2003 | nafamostat mesylate | several human pancreatic cancer cell lines | antagonizing TAT-induced activation of PAR-2 | inhibition of tumor cell growth and invasion |
|
| ||||
| Uwagawa et al. [53] 2009 | (1) nafamostat mesylate
(2) nafamostat mesylate plus gemcitabine |
human pancreatic cancer cell line (Panc-1) | Down-regulation of NF-κB with reduction of ICAM-1, IL-8, VEGF, MMP-9, uPA, RRM1 | (1) inhibition of tumor cell adhesion and growth, angiogenesis, invasion metastasis (2) increase of apoptosis (3) increase of body weight loss of mice |
|
| ||||
| Uwagawa et al. [54] 2009 | nafamostat mesylate plus intra-arterial gemcitabine | unresectable locally advanced or metastatic pancreatic cancer (20 pts) |
not analyzed | (1) CBR of 60% (2) reduction of CA19-9 serum level in 90% of pts (3) improvement in health-related quality of life |
|
| ||||
| Fujiwara et al. [55] 2011 | nafamostat mesylate | human pancreatic cancer cell lines (AsPC-1, BxPC-3, PANC-1) |
down-regulation of IkBα, NF-κB with reduction of ICAM-1, IL-8, VEGF, MMP-9, uPA | (1) increase of cell adhesion, programmed cell death (2) inhibition of angiogenesis, invasion, metastasis in peritoneal dissemination |
|
| ||||
| Gocho et al. [56] 2013 | (1) nafamostat mesylate
(2) nafamostat mesylate plus oxaliplatin |
human pancreatic cancer cell line (Panc-1) and pancreatic cancer mouse model |
down-regulation of NF-κB with reduction of ICAM-1, IL-8, VEGF, MMP-9, uPA, c-IAP1, c-IAP2 | (1) increase of cell adhesion, caspase-8-mediated apoptosis (2) inhibition of PARP, angiogenesis, invasion and metastasis, (3) synergistic cytotoxic effect |
PAR-2, Protease-activated receptor-2; MAPK, mitogen-activated protein kinase; COX, cyclooxygenase; IL, Interleukin; GM-CSF, Granulocyte-macrophage colony stimulating factor; TAT, Tumor-associated trypsinogen; IkB, Inhibitor of NF-κB; NF-κB, Nuclear factor-kappaB; MMPs, metalloproteinases; uPA, urokinase-type plasminogen activator; ICAM-1, Intercellular Adhesion Molecule-1, VEGF, Vascular endothelial growth factor, IAP, Inhibitors of apoptosis.