ArticleCancer chemotherapy and pharmacology2024
Continuous exposure to doxorubicin induces stem cell-like characteristics and plasticity in MDA-MB-231 breast cancer cells identified with the SORE6 reporter.
Article in Cancer chemotherapy and pharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- A Ferrous-Supply-Regenerating Lipid Nanoparticle Integrating RNAi Induces Ferroptosis for Cancer Therapy.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Article
- Targeted delivery of doxorubicin using RSV F-protein modified breast cancer-derived exosomes in breast cancer-bearing mice.BioImpacts : BI · 2026Article
- Interfacial Stress Regulates Plasticity and Drug Resistance at the Breast Cancer-Host Interface.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Molecular and phenotypic characterization of 5-FU resistant colorectal cancer cells: toward enrichment of cancer stem cells.Cancer cell international · 2025Article
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Authors and funding
6 authors.
Funding
Abstract
purposeCancer stem cells (CSCs) account for recurrence and resistance to breast cancer drugs, rendering them a cause of mortality and therapeutic failure. In this study, we examined the effects of exposure to low concentrations of doxorubicin (Dox) on CSCs and non-CSCs from TNBC.
methodsThe effects of Dox were studied using the SORE6 reporter system. We examined the enrichment of the CSCs population, as well as the proliferation, and death of the reporter-positive fraction (GFP + cells) by flow cytometry. The resistant and stemness phenotypes were analyzed by viability and mammosphere formation assay, respectively. We identified differentially expressed and coregulated genes by RNA-seq analysis, and the correlation between gene expression and clinical outcome was evaluated by Kaplan-Mayer analysis using public databases.
resultsIn MDAMB231 and Hs578t cells, we identified enriched subsets in the CSCs population after continuous exposure to low concentrations of Dox. Cells from these enriched cultures showed resistance to toxic concentrations of Dox and increased efficiency of mammosphere formation. In purified GFP + or GFP- cells, Dox increased the mammosphere-forming efficiency, promoted phenotypic switches in non-CSCs populations to a CSC-like state, reduced proliferation, and induced differential gene expression. We identified several biological processes and molecular functions that partially explain the development of doxorubicin-resistant cells and cellular plasticity. Among the genes that were regulated by Dox exposure, the expression of ITGB1, SNAI1, NOTCH4, STAT5B, RAPGEF3, LAMA2, and GNAI1 was significantly associated with poor survival, the stemness phenotype, and chemoresistance.
conclusionThe generation of chemoresistant cells that have characteristics of CSCs, after exposure to low concentrations of Dox, involves the differential expression of genes that have a clinical impact.
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