Antitumor effects of Nafamostat mesilate on head and neck squamous cell carcinoma.
OBJECTIVE
Nafamostat mesilate (FUT-175), a synthetic serine protease inhibitor, has antitumor activities toward adenocarcinoma, e.g., colon cancer. However, its antitumor effects on other types of cancer have been less extensively studied. We investigated the biological activities of Nafamostat mesilate on cell proliferation, cell-invasive potential and growth factor production in head and neck squamous cell carcinoma (HNSCC).


METHODS
Two human HNSCC cell lines established in our department, YCU-L891 and -H891, and a human vulvar squamous cell carcinoma cell line, A431, were examined for the effect of Nafamostat mesilate. The effects on cell growth were evaluated using the MTT assay. The effects on the relative expression levels of mRNA were measured by quantitative RT-PCR. Cytokine secretion was analyzed by enzyme-linked immunosorbent assay.


RESULTS
Nafamostat mesilate inhibited the proliferation of two HNSCC cell lines, YCU-L891 and YCU-H891, and A431. In these cell lines, Nafamostat mesilate down-regulated both matrix metalloproteinase (MMP)-2 and -9. In addition, it reduced the productions of vascular endothelial growth factor (VEGF) and transforming growth factor beta1 (TGF-beta1) by the tumor cells.


CONCLUSIONS
Our results suggest that Nafamostat mesilate has potential for use as a treatment against local growth, invasion and metastasis of squamous cell carcinoma.
Yamashita
Yukiko
Y
Department of Biology and Function in the Head and Neck, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. t036048f@med.yokohama-cu.ac.jp
Ishiguro
Yukari
Y
Sano
Daisuke
D
Kimura
Machiko
M
Fujita
Kyoko
K
Yoshida
Takafumi
T
Horiuchi
Choichi
C
Taguchi
Takahide
T
Matsuda
Hideki
H
Mikami
Yasukazu
Y
Tsukuda
Mamoru
M
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001550:Benzamidines; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology*; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000235:genetics / Q000473:pathology*; D066298:In Vitro Techniques; D007822:Laryngeal Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000473:pathology; D014410:Tumor Stem Cell Assay; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D014846:Vulvar Neoplasms / Q000473:pathology
D000970:Antineoplastic Agents; D001550:Benzamidines; D006146:Guanidines; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C032855:nafamostat