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Signal transducer and activator of transcription 3 (STAT3) is involved in the growth and metastasis of breast cancer,and represents a potential target for developing new anti-tumor drugs.The purpose of this study is to investigate whether Lycorine,a pyrrolo[de]phenanthridine ring-type alkaloid extracted from Amaryllidaceae genera,could inhibit breast cancer by targeting STAT3 signaling pathway.The human breast cancer cell lines were incubated with various concentrations of Lycorine,and cell proliferation,colony formation,cell cycle distribution,apoptosis,migration and invasion were assayed by several in vitro approaches.Results showed that Lycorine significantly suppressed cell proliferation,colony formation,migration and invasion,as well as induced cell apoptosis,but showed no apparent impact on cell cycle.In addition,the effect of Lycorine on tumor growth and metastasis in nude mouse models was investigated,and results showed that Lycorine significantly inhibited tumor growth and metastasis in vivo.Mechanistically,Lycorine significantly inhibited STAT3 phosphorylation and transcriptional activity through upregulating SHP-1 expression.Lycorine also downregulated the expressions of STAT3 target genes,including Mcl-1,Bcl-xL,MMP-2,MMP-9,which are involved in apoptosis and invasion of breast cancer.Taken together,these findings suggest that Lycorine may be a promising candidate for the prevention and treatment of human breast cancer.