Liuwei Dihuang pill suppresses metastasis by regulating the wnt pathway and disrupting -catenin/T cell factor interactions in a murine model of triple-negative breast cancer.

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, ß-catenin, T cell factor (TCF), cyclin- D1 and vascular endothelial growth factor (VEGF) was detected by western blotting or immunofluorescence. ß-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, ß-catenin, cyclin-D1 and VEGF was decreased, and ß-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 ß-catenin/TCF-1 interactions in the Wnt pathway.