Abstract
Previously, berberine enhanced the sensitivity of MCF-7-resistant breast cancer cells toward tamoxifen; however, its molecular mechanism still remains unclear. The purpose of this study is to identify the potential targets and molecular mechanism of berberine in overcoming breast cancer resistance toward tamoxifen by using a bioinformatics approach for functional network analysis. The microarray data of tamoxifen-resistant and berberine-treated MCF-7 cells were obtained from GSE67916 and GSE85871, which resulted in differentially expressed genes (DEGs). The analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment by using The Database for Annotation, Visualization and Integrated Discovery (DAVID) revealed that several DEGs participated in the erbB tyrosine kinase signaling pathway. The analysis of protein–protein interaction network and hub genes selection by using STRING and Cytoscape identified the top 10 genes with the highest degree score. The analysis of genetic alterations by using cBioportal demonstrated genetic alterations of six potential target genes including PRKCA, EGFR, ERBB4, AREG, ESR1, and STAT1. Moreover, importantly, the erbB signaling is a potential target for overcoming breast cancer resistance toward tamoxifen. Further studies are required to validate the results of this study.
Highlights
Breast cancer was one of the primary reasons for death among women worldwide in 2018 (Bray et al, 2018)
The purpose of this study is to identify the potential targets and molecular mechanisms of berberine in overcoming breast cancer resistance toward tamoxifen by using a bioinformatics approach for functional network analysis
The analysis of genetic alterations by using cBioPortal demonstrated the genetic alterations of six potential target genes, including protein kinase C alpha type (PRKCA), epidermal growth factor receptor (EGFR), erb-b2 receptor tyrosine kinase 4 (ERBB4), amphiregulin (AREG), estrogen receptor 1 (ESR1), and signal transducer and activator of transcription 1 (STAT1)
Summary
Breast cancer was one of the primary reasons for death among women worldwide in 2018 (Bray et al, 2018). Endocrine therapy, including tamoxifen, has demonstrated the effectiveness of luminal A breast cancer treatment (Lindström et al, 2018). Despite its successful development as ER-targeted therapy, patients developed resistance toward tamoxifen, further leading to relapse and metastasis (Viedma-Rodriguez et al, 2014). The previous studies demonstrated that berberine exhibited an anticancer activity on various types of cancer including breast cancer (Tak et al, 2019), colorectal cancer (Palmieri et al, 2019), lung cancer (Zhu et al, 2015), ovarian cancer, prostate cancer, liver cancer, and cervical cancer (Liu et al, 2019). The molecular mechanism of berberine in circumventing tamoxifen resistance remains unclear
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