Abstract: OBJECTIVE: To investigate if the Liuwei Dihuang pill(LWDHP) can inhibit metastasis to the liver and lungs in mice bearing triple-negative breast cancer(TNBC), and the molecular mechanism underpinning this action.METHODS: Ninety-nine TNBC bearing-mice were distributed randomly to five groups: control(Con),paclitaxel(PTX), low-dose LWDHP(LLP, 2.3 g·kg~(-1)·d~(-1)), middle-dose LWDHP(MLP, 4.6 g·kg~(-1)·d~(-1))and high-dose LWDHP(HLP, 9.2 g·kg~(-1)·d~(-1)). The LWDHP were administered(p.o.) to the agonal stage. The morphology of BC cells was observed by hematoxylin & eosin staining. Expression of axin-2,β-catenin, T cell factor(TCF), cyclin-D1 and vascular endothelial growth factor(VEGF) was detected by western blotting or immunofluorescence.β-catenin/TCF-1 interaction was measured using a co-immunoprecipitation assay.RESULTS: After LWDHP treatment, metastasis of BC cells to the lungs and liver was inhibited, expression of axin-2 was increased, expression of TCF-1,β-catenin, cyclin-D1 and VEGF was decreased, andβ-catenin/TCF-1 interaction was disrupted.CONCLUSION: The LWDHP could inhibit metastasis of BC cells to the liver and lungs. The molecular mechanism underlying this action may be regulation of protein expression and β-catenin/TCF-1 interactions in the Wnt pathway.

Key words: Triple negative breast neoplasms, Neoplasm metastasis, Beta catenin, T cell transcription factor 1, Wnt signaling pathway, Liuwei Dihuang pill