Nafamostat mesilate negatively regulates the metastasis of triple-negative breast cancer cells

다국어 초록 (Multilingual Abstract)

Triple-negative breast cancer (TNBC) lacking ofoestrogen receptor, progesterone receptor, and epidermalgrowth factor receptor type 2 is a highly malignant diseasewhich results in a poor prognosis and rare treatmentoptions. Despite the use of conventional chemotherapy forTNBC tumours, resistance and short duration responseslimit the treatment efficacy. Therefore, a need exists todevelop a new chemotherapy for TNBC. The aim of thisstudy was to examine the anti-cancer effects of nafamostatmesilate (NM), a previously known serine protease inhibitorand highly safe drug on breast cancer cells. Here, weshowed that NM significantly inhibits proliferation,migration, and invasion in MDA-MB231 cells, induces G2/M phase cell-cycle arrest, and inhibits the expression ofcyclin-dependent kinase 1 (CDK1). Exposure of MDAMB231cells to NM also resulted in decreased transcriptionfactor activities accompanied by the regulated phosphorylationof signalling molecules and a decrease in metalloproteinases,the principal modulators of the extracellularenvironment during cancer progression. Especially, inhibitionof TGFb-stimulated Smad2 phosphorylation andsubsequent metastasis-related gene expression, and downregulationof ERK activity may be pivotal mechanismsunderlying inhibitory effects of NM on NM inhibits lungmetastasis of breast cancer cells and growth of colonizedtumours in mice. Taken together, our data revealed thatNM inhibits cell growth and metastasis of TNBC cells andindicated that NM is a multi-targeted drug that could be anadjunct therapy for TNBC treatment.

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