Antimetastasis Effect of Astragalus membranaceus-Curcuma zedoaria via β-Catenin Mediated CXCR4 and EMT Signaling Pathway in HCT116

Xiying Tan,Ming Xu,Fuyan Liu,Decai Tang,Mengting Xu,Yi Yao

doi:10.1155/2019/9692350

Abstract

Astragalus membranaceus and Curcuma zedoaria, two traditional Chinese medicines, are widely used together in colorectal cancer adjuvant treatment. Many different mechanisms should be involved in the benefit effect of Astragalus membranaceus and Curcuma zedoaria. In this study, we established that the combined extract from Astragalus membranaceus and Curcuma zedoaria (HQEZ) decreased the metastasis ability in colorectal cancer cells (HCT116, a cell line of colorectal carcinoma established from Homo sapiens) in vitro, and the treatment induced the downregulation of EMT signal and decreased CXCR4 expression and the level of β-catenin. Overexpression of CXCR4 and the administration of the agonist and inhibitor to β-catenin signal pathway were used to explore the mechanism of Astragalus membranaceus and Curcuma zedoaria in colorectal cancer treatment. The data demonstrated that HQEZ increased the phosphorylation of β-catenin which related to the degradation of β-catenin, and it induced the downregulation of EMT signal and CXCR4. It meant that the influence of β-catenin should be a key event in the antimetastasis effects of Astragalus membranaceus-Curcuma zedoaria in colorectal cancer model. These findings revealed the potential effect and mechanism of Astragalus membranaceus-Curcuma zedoaria in colorectal cancer treatment and provided insight for optimization of the usage.

Highlights

Colorectal cancer, the fourth most common cancer, affects more than one million people per year and causes more than 600000 deaths in world [1]
We found HQEZ decreased the expression of CXCR4 in colorectal cancer cells, and we found the inhibition of EMT and β-catenin
HQEZ induces the degradation of βcatenin in a relatively low concentration and inhibits the metastasis of colorectal cancer cells in vitro. These results provide a potential mechanism of traditional Chinese medicine used in colorectal cancer treatment and pursue HQEZ as an adjuvant therapy used to colorectal cancer patients

Summary

Introduction

Colorectal cancer, the fourth most common cancer, affects more than one million people per year and causes more than 600000 deaths in world [1]. Chemotherapy is a common adjuvant therapy which increases median overall survival especially in combination chemotherapy, whereas patients’ performance status is usually not good enough to tolerate combination chemotherapy [1, 3]. Other adjuvant therapies, such as antibody therapy targeting VEGF or EGFR and immunotherapy, are widely used and are efficacious in patients [1, 3], but the sensitivity relates to special biomarkers. Researching the relationship between the compatibility and the effect may provide more information about the compatibility and/or ratio of known/unknown active ingredients

Results

Discussion

Conclusion