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

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

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)

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.

Original languageEnglish
Article number10791
Number of pages13
JournalScientific Reports
Volume11
Issue number1
DOIs
Publication statusPublished - Dec 2021
Externally publishedYes

Fingerprint

Dive into the research topics of 'The inhibition of ABCB1/MDR1 or ABCG2/BCRP enables doxorubicin to eliminate liver cancer stem cells'. Together they form a unique fingerprint.

Cite this