Nafamostat Mesilate（ FUT-175） Inhibits Cell Growth and Invasion of Malignant Pleural Mesothelioma Cell Line, MSTO-211H

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Nafamostat mesilate（ FUT-175）, a synthetic serine protease inhibitor, has been reported to have antitumouractivities toward solid tumours. The objective of this study was to characterize the biological activities of FUT-175 ina malignant mesothelioma cell line. We used MSTO-211H, a biphasic-type human malignant pleural mesothelioma cellline. The effect on cell growth was evaluated by 3（- 4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide assay.Secretion of urokinase-type plasminogen activator（ u-PA） and plasminogen activator inhibitor-1（ PAI-1） was analysedby enzyme-linked immunosorbent assay. The eff ects on relative mRNA expression levels were measured by reversetranscription polymerase chain reaction. The eff ect on cell invasiveness was evaluated by cell invasion assay. FUT-175at 10-5 M signifi cantly inhibited cell growth and cell invasiveness. Cell growth reduced to 47.0 ± 2.1% compared withthe control. The number of invasive cells also reduced to 16.0 ± 0.7 cells/hpf, while that of control cells was 41.4 ± 8.0cells /hpf. U-PA and PAI-1 secreted from the cells were also reduced by FUT-175 in a dose-dependent manner. Theseresults suggest that FUT-175 has the potential to act as a therapeutic agent against local growth and invasion, andfunctions by reducing PAI-1 and u-PA production of the human malignant mesothelioma（195 words）