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.

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.

Effect of Liuweidihuang pill and Jinkuishenqi pill on inhibition of spontaneous breast carcinoma growth in mice.

OBJECTIVE: To investigate the preventing and treating action of Liuweidihuang pill (LP) and Jinkuishenqi pill (JP) on spontaneous breast carcinoma in mice. METHODS: A model of spontaneous breast carcinoma was derived from 11.5-month-old female Kunming breeding mice following the delivery of several litters. The mice were randomly divided into five groups: model control group (C), Liuweidihuang pill high-dose group (LH; 4.6 g · kg(-1) · d(-1)), Liuweidihuang pill low-dose group (LL; 2.3 g · kg(-1) · d(-1)), Jinkuishenqi pill high-dose group (JH; 4.6 g · kg(-1) · d(-1)) and Jinkuishenqi pill low-dose group (JL; 2.3 g · kg(-1) · d(-1)). Cancer tissue volume was measured by water immersion. Histopathology was analyzed by hematoxylin and eosin staining. Vascular endothelial growth factor (VEGF), extracellular signal-regulated kinase (ERK) and cyclin D1 protein expression in cancer tissue was assayed by western blotting. RESULTS: Compared with the control group, cancer tissue volume and weight were lower in the LP and JP groups, and survival time was longer. The expression of VEGF, ERK and Cyclin D1 were inhibited in the LP and JP groups (P < 0.05), and cell differentiation was increased. Tumor weights and volumes and VEGF, ERK and Cyclin D1 expression in LL or LH were significantly lower than in JL and JH (P < 0.01). CONCLUSION: Both LP and JP could restrain cancer growth and promote cancer cell differentiation; moreover, LP was more effective than JP The likely mechanism of action was via inhibition of VEGF, ERK and cyclin D1.