ZOU Le-lan, LIU Hong-ning, LYU Hong, et al. Anti-metastatic Effect of Zuoguiwan on Breast Cancer Cells and Its Mechanisms of Action[J]. Chinese journal of experimental traditional medical formulae, 2017, 23(23): 85-90.
DOI:
ZOU Le-lan, LIU Hong-ning, LYU Hong, et al. Anti-metastatic Effect of Zuoguiwan on Breast Cancer Cells and Its Mechanisms of Action[J]. Chinese journal of experimental traditional medical formulae, 2017, 23(23): 85-90. DOI: 10.13422/j.cnki.syfjx.2017230085.
Anti-metastatic Effect of Zuoguiwan on Breast Cancer Cells and Its Mechanisms of Action
Objective: To investigate the anti-metastatic effect of Zuoguiwan and its mechanisms of action. Method: The bone marrow metastasis mode of nude mice was established by intra-femoral injection. The tumor-bearing mice were randomly divided into three groups:control group
low-dose Zuoguiwan (21 g·kg-1 per day) treatment group and high-dose Zuoguiwan (42 g·kg-1 per day) treatment group. After successive administration for 8 weeks
the expression of human ck19 gene was detected by nest polymerase chain reaction (PCR) assay to determine the metastatic foci of MDA-MB-231 cells in bone marrow. Oris migration assay was performed to determine the effect of Zuoguiwan-containing sera on the migration of MDA-MB-231 cells. Reconstituted basement membrane invasion assay was conducted to decide the effect of Zuoguiwan-containing sera on the invasion of MDA-MB-231 cells. F-actin polymerization was detected with Alexa Fluor® 488 phalloidin and fluorescence microscopy. The effect of Zuoguiwan-containing sera on parathyroid hormone-related protein (PTHrP) and C-X-C chemokine receptor type 4 (CXCR4) expressions in MDA-MB-231 was determined by Western blot assay. Result: Compared with control group
both low-dose Zuoguiwan group and high-dose Zuoguiwan group exhibited a significant suppression on the expression of ck19 gene in bone marrow of tumor-bearing mice (P<0.01). Data from Oris migratory assay showed that Zuoguiwan-containing sera inhibited transforming growth factor-beta (TGF-β)-induced migration in MDA-MB-231 cells significantly. It was also found that the invasive ability of MDA-MB-231 cells through reconstituted basement membrane was inhibited by Zuoguiwan-containing sera in reconstituted basement membrane invasion assay. The amount of invaded cells in Zuoguiwan-containing sera treatment groups was less than that in control group obviously (P<0.01). Data from fluorescence assay showed that Zuoguiwan-containing sera inhibited F-actin polymerization of breast cancer cells. It was also showed that Zuoguiwan-containing sera suppressed the expressions of PTHrP and CXCR4 in Western blot assay
significantly. Conclusion: Zuoguiwan has a significant anti-metastatic effect on breast cancer cells. Its mechanism of action is correlated with the suppression on motility of breast cancer cells
and the down-regulation of PTHrP and CXCR4 expressions.