Triple-negative breast cancer (TNBC) lacking of oestrogen
receptor, progesterone receptor, and
epidermal growth factor receptor type 2 is a highly malignant disease which results in a poor prognosis and rare treatment options. Despite the use of conventional
chemotherapy for TNBC tumours, resistance and short duration responses limit the treatment efficacy. Therefore, a need exists to develop a new
chemotherapy for TNBC. The aim of this study was to examine the anti-
cancer effects of
nafamostat mesilate (NM), a previously known
serine protease inhibitor and highly safe drug on
breast cancer cells. Here, we showed that NM significantly inhibits proliferation, migration, and invasion in MDA-MB231 cells, induces G2/M phase cell-cycle arrest, and inhibits the expression of
cyclin-dependent kinase 1 (CDK1). Exposure of MDA-MB231 cells to NM also resulted in decreased
transcription factor activities accompanied by the regulated phosphorylation of signalling molecules and a decrease in
metalloproteinases, the principal modulators of the extracellular environment during
cancer progression. Especially, inhibition of TGFβ-stimulated Smad2 phosphorylation and subsequent
metastasis-related gene expression, and downregulation of ERK activity may be pivotal mechanisms underlying inhibitory effects of NM on NM inhibits lung
metastasis of
breast cancer cells and growth of colonized tumours in mice. Taken together, our data revealed that NM inhibits cell growth and
metastasis of TNBC cells and indicated that NM is a multi-targeted drug that could be an adjunct
therapy for TNBC treatment.