Abstract

BackgroundXihuang Pill (XHP) is mainly used to treat “Ru Yan (breast cancer)”. Evidence-based medical evidence and showed that XHP improves the efficacy of chemotherapy and reduced chemotherapy-induced toxicity in breast cancer patients. However, the mechanism of XHP against breast cancer is not clear.MethodsThe effect of XHP extract on cell half-inhibitory concentration (IC50) and cell viability of MD-MB-231 cells was detected by CCK-8 method. The cell inhibition rate of MDA-MB-453 cells were detected by MTT method. Apoptosis was detected by flow cytometry, cell transfer ability was detected by Transwell method, and cell proliferation ability was detected by colony formation assay. The expression of Notch1, β-catenin and c-myc mRNA in MDA-MB-453 cells were detected by real-time fluorescence quantitative PCR. Then, chemical informatics and transcriptomics methodology was utilized to predict the potential compounds and targets of XHP, and collect triple negative breast cancer (TNBC) genes and the data of Olibanum and β-boswellic acid intervention MD-MB-231 cells (from GSE102891). The cytoscape software was utilized to undergo network construction and network analysis. Finally, the data from the network analysis was imported into the DAVID database for enrichment analysis of signaling pathways and biological processes.ResultsThe IC50 was 15.08 g/L (for MD-MB-231 cells). After interfering with MD-MB-231 cells with 15.08 g/L XHP extract for 72 h, compared with the control group, the cell viability, migration and proliferation was significantly decreased, while early apoptosis and late apoptosis were significantly increased (P < 0.01). After interfering with MDA-MB-453 cells with 6 g/L XHP extract for 72 h, compared with the control group, the cell inhibition and apoptosis rate increased, while the expression of Notch1, β-catenin and c-myc mRNA decreased. (P < 0.05). The chemical informatics and transcriptomics analysis showed that four networks were constructed and analyzed: (1) potential compounds-potential targets network of XHP; (2) XHP-TNBC PPI network; (3) DEGs PPI network of Olibanum-treated MD-MB 231 cells; (4) DEGs PPI network of β-boswellic acid -treated MD-MB 231 cells. Several anti-TNBC biological processes, signaling pathways, targets and so on were obtained.ConclusionXHP may exert anti-TNBC effects through regulating biological processes, signaling pathways, targets found in this study.

Highlights

  • Breast cancer is the leading cause of death among women worldwide, and the incidence rate has increased significantly in recent years, which seriously threatens women’s health (Fan et al, 2014; Desantis et al, 2017)

  • Inhibition Effect of Xihuang Pill (XHP) on the Growth of MD-MB231 Cell Different concentrations of XHP were applied to MD-MB-231 cells for 72 h, and the OD value of each group was detected by CCK-8 kit

  • 6 g/L was selected as the non-cytotoxic concentration of XHP for subsequent MDA-MB-453 experiments

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Summary

Introduction

Breast cancer is the leading cause of death among women worldwide, and the incidence rate has increased significantly in recent years, which seriously threatens women’s health (Fan et al, 2014; Desantis et al, 2017). Breast cancer is currently divided into five subtypes by coding sequence microarray technology (Prat et al, 2015; Cejalvo et al, 2018): (1) Luminal-A type; (2) Luminal-B type; (3) human epidermal growth factor receptor 2 (HER2) overexpression type; (4) base-like type; (5) normal type. Basal-like breast cancer is non-specific invasive ductal carcinoma (Jiang et al, 2019), and its ER, PR and HER2 are negative, known as triple negative breast cancer (TNBC). The vast majority of TNBCs are highly invasive ductal carcinomas with nuclear polymorphism, high mitotic rate, and minimal tubule formation (Kulkarni et al, 2019). Evidence-based medical evidence and showed that XHP improves the efficacy of chemotherapy and reduced chemotherapy-induced toxicity in breast cancer patients. The mechanism of XHP against breast cancer is not clear

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