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Breast cancer is one of the most common malignancies that threaten the health of women. Although there are a few chemotherapies for the clinical treatment of breast cancer, these therapies are faced with the problems of drug‑resistance and metastasis. Drug combination can help to reduce the adverse side effects of chemotherapies using single drugs, and also help to overcome common drug‑resistance during clinical treatment of breast cancer. The present study reported the synergistic effect of the heat shock protein 90 inhibitor 17‑AAG and the histone deacetylase 6 inhibitor Belinostat in triple‑negative breast cancer (TNBC) MDA‑MB‑231 cells, by detection of proliferation, apoptosis and cell cycle arrest following treatment with this combination. Subsequently, RNA sequencing (RNA‑seq) data was collected and analyzed to investigate the synergistic mechanism of this combination. Based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways revealed by RNA‑seq data analysis, a wound‑healing assay was used to investigate the effect of this combination on the migration of MDA‑MB‑231 cells. Compared with treatment with 17‑AAG or Belinostat alone, both the viability inhibition and apoptosis rate of MDA‑MB‑231 cells were significantly enhanced in the combination group. The combination index values were <1 in three concentration groups. Revealed by the RNA‑seq data analysis, the most significantly enriched KEGG pathways in the combination group were closely associated with cell migration. Based on these findings, the anti‑migration effect of this combination was investigated. It was revealed that the migration of MDA‑MB‑231 cells was significantly suppressed in the combination group compared with in the groups treated with 17‑AAG or Belinostat alone. In terms of specific genes, the mRNA expression levels of TEA domain family proteins were significantly decreased in the combination group, whereas the phosphorylation of YY1 associated protein 1 and modulator of VRAC current 1 was significantly enhanced in the combination group. These alterations may help to explain the anti‑migration effect of this combination. Belinostat has already been approved as a treatment for T‑cell lymphoma and 17‑AAG is undergoing clinical trials. These findings could provide a beneficial reference for the clinical treatment of patients with TNBC.
Pubmed ID: 32236631
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Software that estimates expression at transcript-level resolution and controls for variability evident across replicate libraries.
View all literature mentionsSoftware repository for R packages related to analysis and comprehension of high throughput genomic data. Uses separate set of commands for installation of packages. Software project based on R programming language that provides tools for analysis and comprehension of high throughput genomic data.
View all literature mentionsGeneAnswers provide an integrated tool for given genes biological or medical interpretation. It includes statistical test of given genes and specified categories. Microarray techniques have been widely employed in genomic scale studies for more than one decade. The standard analysis of microarray data is to filter out a group of genes from thousands of probes by certain statistical criteria. These genes are usually called significantly differentially expressed genes. Recently, next generation sequencing (NGS) is gradually adopted to explore gene transcription, methylation, etc. Also a gene list can be obtained by NGS preliminary data analysis. However, this type of information is not enough to understand the potential linkage between identified genes and interested functions. The integrated functional and pathway analysis with gene expression data would be very helpful for researchers to interpret the relationship between the identified genes and proposed biological or medical functions and pathways. The GeneAnswers package provides an integrated solution for a group of genes and specified categories (biological or medical functions, such as Gene Ontology, Disease Ontology, KEGG, etc) to reveal the potential relationship between them by means of statistical methods, and make user-friendly network visualization to interpret the results. Besides the package has a function to combine gene expression profile and category analysis together by outputting concept-gene cross tables, keywords query on NCBI Entrez Gene and application of human based Disease ontology analysis of given genes from other species can help people to understand or discover potential connection between genes and functions. Sponsors: This project was supported in part by Award Number UL1RR025741 from the National Center for Research Resources.
View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsIntegrated database resource consisting of 16 main databases, broadly categorized into systems information, genomic information, and chemical information. In particular, gene catalogs in completely sequenced genomes are linked to higher-level systemic functions of cell, organism, and ecosystem. Analysis tools are also available. KEGG may be used as reference knowledge base for biological interpretation of large-scale datasets generated by sequencing and other high-throughput experimental technologies.
View all literature mentionsSoftware tool for transcriptome assembly and differential expression analysis for RNA-Seq. Includes script called cuffmerge that can be used to merge together several Cufflinks assemblies. It also handles running Cuffcompare as well as automatically filtering a number of transfrags that are likely to be artifacts. If the researcher has a reference GTF file, the researcher can provide it to the script to more effectively merge novel isoforms and maximize overall assembly quality.
View all literature mentionsOpen source software package for statistical programming language R to create plots based on grammar of graphics. Used for data visualization to break up graphs into semantic components such as scales and layers.
View all literature mentionsCell line MCF-10A is a Spontaneously immortalized cell line with a species of origin Homo sapiens
View all literature mentionsCell line MDA-MB-231 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MCF-7 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line BT-549 is a Cancer cell line with a species of origin Homo sapiens (Human)
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