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.

Cancer stem cells (CSCs) play a critical role in both cancer initiation and relapse as they are resistant to most cytotoxic agents and able to proliferate indefinitely. The plant alkaloid oxymatrine has many biological activities including the ability to induce cell cycle arrest and apoptosis, which makes it a potentially useful agent for targeting cancer cells. In order to determine whether it has beneficial pharmacological properties to eradicate CSCs, we analyzed the effects of oxymatrine on MCF-7 breast cancer cells. Cancer stem-like cells' (side population, SP) identification and sorting were performed. The inhibitory effect of oxymatrine was evaluated on the sorted SP and non-SP cells. The results indicated that oxymatrine caused a dose-dependent reduction in the proliferation of MCF-7 cells and a decrease in SP cells. Wnt/β-catenin signaling pathway was also examined by analyzing the expression of total β-catenin and phosphorylated β-catenin in cytoplasm, and the results showed that the growth inhibitory effects of oxymatrine treatment on MCF-7 cells may be due to the inhibition of SP and Wnt/β-catenin signaling pathway. Further work is warranted to explore whether oxymatrine may be a useful novel therapeutic drug for targeting breast CSCs.