The inhibition of ABCB1/MDR1 or ABCG2/BCRP enables doxorubicin to eliminate liver cancer stem cells

W. Yin; D. Xiang; T. Wang; Y. Zhang; C.V. Pham; S. Zhou; G. Jiang; Y. Hou; Y. Zhu; Y. Han; L. Qiao; P.H-L. Tran; W. Duan

doi:10.1038/s41598-021-89931-9

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The inhibition of ABCB1/MDR1 or ABCG2/BCRP enables doxorubicin to eliminate liver cancer stem cells

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The inhibition of ABCB1/MDR1 or ABCG2/BCRP enables doxorubicin to eliminate liver cancer stem cells

W. Yin, D. Xiang, T. Wang, Y. Zhang, C.V. Pham, S. Zhou, G. Jiang, Y. Hou, Y. Zhu, Y. Han, …

Scientific Reports, Vol.11(1), Art. 10791

2021

DOI: https://doi.org/10.1038/s41598-021-89931-9

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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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Title: The inhibition of ABCB1/MDR1 or ABCG2/BCRP enables doxorubicin to eliminate liver cancer stem cells
Authors/Creators: W. Yin (Author/Creator) - Deakin University
D. Xiang (Author/Creator) - State Key Laboratory of Oncogene and Related Genes
T. Wang (Author/Creator) - Murdoch University
Y. Zhang (Author/Creator) - Deakin University
C.V. Pham (Author/Creator) - Deakin University
S. Zhou (Author/Creator) - Huaqiao University
G. Jiang (Author/Creator) - Second Affiliated Hospital of Soochow University
Y. Hou (Author/Creator) - Shaanxi Normal University
Y. Zhu (Author/Creator) - Suzhou Institute of Nano-tech and Nano-bionics
Y. Han (Author/Creator) - Shanghai OneTar Biomedicine, Shanghai, 201203, China.
L. Qiao (Author/Creator) - Westmead Institute
P.H-L. Tran (Author/Creator) - Deakin University
W. Duan (Author/Creator) - Deakin University
Publication Details: Scientific Reports, Vol.11(1), Art. 10791
Publisher: Springer Nature
Identifiers: 991005540434607891
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