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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/67c194d8536544da957644e48e94460b
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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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The inhibition of ABCB1/MDR1 or ABCG2/BCRP enables doxorubicin to eliminate liver cancer stem cells

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