Journal article
The inhibition of ABCB1/MDR1 or ABCG2/BCRP enables doxorubicin to eliminate liver cancer stem cells
Scientific Reports, Vol.11(1), Art. 10791
2021
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.
Details
- Title
- The inhibition of ABCB1/MDR1 or ABCG2/BCRP enables doxorubicin to eliminate liver cancer stem cells
- Authors/Creators
- W. Yin (Author/Creator) - Deakin UniversityD. Xiang (Author/Creator) - State Key Laboratory of Oncogene and Related GenesT. Wang (Author/Creator) - Murdoch UniversityY. Zhang (Author/Creator) - Deakin UniversityC.V. Pham (Author/Creator) - Deakin UniversityS. Zhou (Author/Creator) - Huaqiao UniversityG. Jiang (Author/Creator) - Second Affiliated Hospital of Soochow UniversityY. Hou (Author/Creator) - Shaanxi Normal UniversityY. Zhu (Author/Creator) - Suzhou Institute of Nano-tech and Nano-bionicsY. Han (Author/Creator) - Shanghai OneTar Biomedicine, Shanghai, 201203, China.L. Qiao (Author/Creator) - Westmead InstituteP.H-L. Tran (Author/Creator) - Deakin UniversityW. Duan (Author/Creator) - Deakin University
- Publication Details
- Scientific Reports, Vol.11(1), Art. 10791
- Publisher
- Springer Nature
- Identifiers
- 991005540434607891
- Copyright
- © 2021 The Authors.
- Murdoch Affiliation
- Centre for Comparative Genomics
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.108 Molecular & Cell Biology - Cancer & Development
- 1.108.591 Cancer Stem Cells
- Web Of Science research areas
- Oncology
- ESI research areas
- Clinical Medicine