Sitravatinib sensitizes ABCB1-and ABCG2-overexpressing multidrug-resistant cancer cells to chemotherapeutic drugs

Chung Pu Wu*, Sung Han Hsiao, Yang Hui Huang, Lang Cheng Hung, Yi Jou Yu, Yu Tzu Chang, Tai Ho Hung, Yu Shan Wu

*此作品的通信作者

研究成果: 期刊稿件文章同行評審

32 引文 斯高帕斯(Scopus)

摘要

The development of multidrug resistance (MDR) in cancer patients driven by the overexpression of ATP-binding cassette (ABC) transporter ABCB1 or ABCG2 in cancer cells presents one of the most daunting therapeutic complications for clinical scientists to resolve. Despite many novel therapeutic strategies that have been tested over the years, there is still no approved treatment for multidrug-resistant cancers to date. We have recently adopted a drug repurposing approach to identify therapeutic agents that are clinically active and at the same time, capable of reversing multidrug resistance mediated by ABCB1 and ABCG2. In the present study, we investigated the effect of sitravatinib, a novel multitargeted receptor tyrosine kinase inhibitor, on human ABCB1 and ABCG2 in multidrug-resistant cancer cell lines. We discovered that at submicromolar concentrations, sitravatinib re-sensitizes ABCB1-and ABCG2-overexpressing multidrug-resistant cancer cells to chemotherapeutic drugs. We found that sitravatinib blocks the drug efflux function of ABCB1 and ABCG2 in a concentration-dependent manner but does not significantly alter the protein expression of ABCB1 or ABCG2 in multidrug-resistant cancer cells. In conclusion, we reveal a potential drug repositioning treatment option for multidrug-resistant cancers by targeting ABCB1 and ABCG2 with sitravatinib and should be further investigated in future clinical trials.

原文英語
文章編號195
期刊Cancers
12
發行號1
DOIs
出版狀態已出版 - 01 2020

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© 2020 by the authors. Licensee MDPI, Basel, Switzerland.

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