Compound Kushen Injection suppresses human breast cancer stem-like cells by down-regulating the canonical Wnt/β-catenin pathway

Weiru Xu,Yingxia Pei,Xinyi Chen,Ying Zhang,Xiaoyun Zhu,Hongsheng Lin,Xin Qi,Liangliang Yang,Wei Hou,Baojin Hua,Zhizheng Zhao

doi:10.1186/1756-9966-30-103

Abstract

BackgroundCancer stem cells (CSCs) play an important role in cancer initiation, relapse and metastasis. To date, no specific medicine has been found to target CSCs as they are resistant to most conventional therapies and proliferate indefinitely. Compound Kushen Injection (CKI) has been widely used for cancer patients with remarkable therapeutic effects in Chinese clinical settings for many years. This study focused on whether CKI could inhibit MCF-7 SP cells in vitro and in vivo.MethodsThe analysis of CKI on SP population and the main genes of Wnt signaling pathway were studied first. Then we studied the tumorigenicity of SP cells and the effects of CKI on SP cells in vivo. The mice inoculated with 10,000 SP cells were randomly divided into three groups (6 in each group) and treated with CKI, cisplatin and saline (as a control) respectively for 7 weeks. The tumor formation rates of each group were compared. The main genes and proteins of the Wnt signaling pathway were analyzed by RT-PCR and western blot.ResultsCKI suppressed the size of SP population (approximately 90%), and down-regulated the main genes of Wnt signaling pathway. We also determined that MCF-7 SP cells were more tumorigenic than non-SP and unsorted cells. The Wnt signaling pathway was up-regulated in tumors derived from SP cells compared with that in tumors from non-SP cells. The tumor formation rate of the CKI Group was 33% (2/6, P < 0.05), and that of Cisplatin Group was 50%(3/6, P < 0.05), whereas that of the Control Group was 100% (6/6).The RT-PCR and western blot results indicated that CKI suppressed tumor growth by down-regulating the Wnt/β-catenin pathway, while cisplatin activated the Wnt/β-catenin pathway and might spare SP cells.ConclusionsIt suggested that CKI may serve as a novel drug targeting cancer stem-like cells, though further studies are recommended.

Highlights

Cancer stem cells (CSCs) play an important role in cancer initiation, relapse and metastasis
Accumulating evidence has indicted that cancer stem cells (CSCs) are the roots of oncogenesis, cancer relapse and metastasis as they are resistant to all conventional therapies, even the advanced targeted therapy [1,2,3,4,5,6]
To determine whether the suppressed cancerstem like cells (SP) cell number decreased with Compound Kushen Injection (CKI) treatment, cells were treated with a range of concentrations of CKI (30, 50, 70 μl/ml) for 48 hours and the SP cells were analyzed by flow cytometry

Summary

Introduction

Cancer stem cells (CSCs) play an important role in cancer initiation, relapse and metastasis. Compound Kushen Injection (CKI) has been widely used for cancer patients with remarkable therapeutic effects in Chinese clinical settings for many years. Accumulating evidence has indicted that cancer stem cells (CSCs) are the roots of oncogenesis, cancer relapse and metastasis as they are resistant to all conventional therapies, even the advanced targeted therapy [1,2,3,4,5,6]. CSCs have been identified in leukemia [7], breast indefinitely and to enrich more tumorigenic cells than other populations. These rare cells have the potential to survive conventional therapeutics and regenerate cancer populations, leading to relapse and metastasis. The underlying anti-cancer mechanisms are not fully understood

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