ArticleScientific reports2021
The inhibition of ABCB1/MDR1 or ABCG2/BCRP enables doxorubicin to eliminate liver cancer stem cells.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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44 citing papers in PubMed, 89 citations in OpenAlex.
- Protease inhibition: breaking the barriers of chemoresistance in cancer.Molecular biology reports · 2026Review
- Cancer Stem Cell Quiescence: Molecular and Microenvironmental Evidence for an Actively Regulated Adaptive Survival Strategy.Cancer medicine · 2026Review
- Milk derived exosomes sensitize Gefitinib-resistant lung cancer cells to Pemetrexed via CAV1-mediated endocytosis.Drug delivery and translational research · 2026Article
- Targeting mTOR with vistusertib attenuates metabolic steatohepatitis and prevents HCC development.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Article
- The Dual Role of ABCG2 Copy Number Variation: A Protective Factor in Cancer Risk, and a Prognostic Marker for Survival in Thai Breast Cancer.Asian Pacific journal of cancer prevention : APJCP · 2026Article
- Cardiac reprogramming via transient overexpression of P-glycoprotein alleviates doxorubicin-induced cardiotoxicity in mice and pigs.Nature communications · 2026Article
- Integrative Transcriptomic and Machine Learning Analysis of ecDNA-Associated Features for Studying Chemotherapy Resistance in TNBC.bioRxiv : the preprint server for biology · 2026Article
- L-Arginine as an Adjuvant Chemosensitizer: Enhancement of Intestinal Permeability and Cytotoxic Activity of Doxorubicin.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Enhanced antitumor activity of atorvastatin and luteolin, with or without doxorubicin, in a solid Ehrlich carcinoma mouse model: modulation of ABC transporters, telomerase, and cancer stem cells.Medical oncology (Northwood, London, England) · 2026Article
- Developing Potent Therapeutics for Liver Cancer Chemoresistance via an RNA Nanotech and Series-Circuit-Christmas-Bulb Mechanism Targeting ABC Transporters.Molecular pharmaceutics · 2026Review
- Drug resistant glioblastoma stem cells exhibit enriched stemness signatures and share extracellular matrix overexpression.BMC cancer · 2025Article
- Combined Photodynamic Therapy and Chemotherapy Using Local Intra-Arterial Intratumoral Administration of Chlorin e6 and Cisplatin: First Clinical Observations.International journal of molecular sciences · 2025Article
- Article
- The role of FOXA1 and miR-212-3p in molecular modulation of doxorubicin resistance in liver cancer.Medical oncology (Northwood, London, England) · 2025Article
- ABCB1 confers resistance to carboplatin by accumulating stem-like cells in the G2/M phase of the cell cycle in p53Cell death discovery · 2025Article
- Photobiomodulation mitigates doxorubicin resistance in MDA-MB-231 breast cancer cells: a promising avenue for overcoming chemoresistance.Lasers in medical science · 2025Article
- PIK3CA mutation fortifies molecular determinants for immune signaling in vascular cancers.Cancer gene therapy · 2025Article
- Cancer stem cells in hepatocellular carcinoma: therapy resistance and emerging treatments.Frontiers in immunology · 2025Review
- Integration of single-nuclei and spatial transcriptomics to decipher tumor phenotype predictive of relapse-free survival in Wilms tumor.Frontiers in immunology · 2025Article
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Authors and funding
13 authors at 8 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Two ATP-binding cassette transporters, ABCB1/MDR1 and ABCG2/BCRP, are considered the most critical determinants for chemoresistance in hepatocellular carcinoma. However, their roles in the chemoresistance in liver cancer stem cells remain elusive. Here we explored the role of inhibition of MDR1 or ABCG2 in sensitizing liver cancer stem cells to doxorubicin, the most frequently used chemotherapeutic agent in treating liver cancer. We show that the inhibition of MDR1 or ABCG2 in Huh7 and PLC/PRF/5 cells using either pharmacological inhibitors or RNAi resulted in the elevated level of intracellular concentration of doxorubicin and the accompanied increased apoptosis as determined by confocal microscopy, high-performance liquid chromatography, flow cytometry, and annexin V assay. Notably, the inhibition of MDR1 or ABCG2 led to the reversal of the chemoresistance, as evident from the enhanced death of the chemoresistant liver cancer stem cells in tumorsphere-forming assays. Thus, the elevation of effective intracellular concentration of doxorubicin via the inhibition of MDR1 or ABCG2 represents a promising future strategy that transforms doxorubicin from a traditional chemotherapy agent into a robust killer of liver cancer stem cells for patients undergoing transarterial chemoembolization.
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