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

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...

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Autores principales: Wang Yin, Dongxi Xiang, Tao Wang, Yumei Zhang, Cuong V. Pham, Shufeng Zhou, Guoqin Jiang, Yingchun Hou, Yimin Zhu, Yinglu Han, Liang Qiao, Phuong H.-L. Tran, Wei Duan
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:67c194d8536544da957644e48e94460b2021-12-02T15:00:51ZThe inhibition of ABCB1/MDR1 or ABCG2/BCRP enables doxorubicin to eliminate liver cancer stem cells10.1038/s41598-021-89931-92045-2322https://doaj.org/article/67c194d8536544da957644e48e94460b2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89931-9https://doaj.org/toc/2045-2322Abstract 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.Wang YinDongxi XiangTao WangYumei ZhangCuong V. PhamShufeng ZhouGuoqin JiangYingchun HouYimin ZhuYinglu HanLiang QiaoPhuong H.-L. TranWei DuanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Wang Yin
Dongxi Xiang
Tao Wang
Yumei Zhang
Cuong V. Pham
Shufeng Zhou
Guoqin Jiang
Yingchun Hou
Yimin Zhu
Yinglu Han
Liang Qiao
Phuong H.-L. Tran
Wei Duan
The inhibition of ABCB1/MDR1 or ABCG2/BCRP enables doxorubicin to eliminate liver cancer stem cells
description 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.
format article
author Wang Yin
Dongxi Xiang
Tao Wang
Yumei Zhang
Cuong V. Pham
Shufeng Zhou
Guoqin Jiang
Yingchun Hou
Yimin Zhu
Yinglu Han
Liang Qiao
Phuong H.-L. Tran
Wei Duan
author_facet Wang Yin
Dongxi Xiang
Tao Wang
Yumei Zhang
Cuong V. Pham
Shufeng Zhou
Guoqin Jiang
Yingchun Hou
Yimin Zhu
Yinglu Han
Liang Qiao
Phuong H.-L. Tran
Wei Duan
author_sort Wang Yin
title The inhibition of ABCB1/MDR1 or ABCG2/BCRP enables doxorubicin to eliminate liver cancer stem cells
title_short The inhibition of ABCB1/MDR1 or ABCG2/BCRP enables doxorubicin to eliminate liver cancer stem cells
title_full The inhibition of ABCB1/MDR1 or ABCG2/BCRP enables doxorubicin to eliminate liver cancer stem cells
title_fullStr The inhibition of ABCB1/MDR1 or ABCG2/BCRP enables doxorubicin to eliminate liver cancer stem cells
title_full_unstemmed The inhibition of ABCB1/MDR1 or ABCG2/BCRP enables doxorubicin to eliminate liver cancer stem cells
title_sort inhibition of abcb1/mdr1 or abcg2/bcrp enables doxorubicin to eliminate liver cancer stem cells
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/67c194d8536544da957644e48e94460b
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