Abstract：
:Pevonedistat is a potent, selective, first-in-class NEDD8 activating enzyme inhibitor. It is now under multiple clinical trials that investigate its anticancer effect against solid tumors and leukemia. ATP-binding cassette (ABC) transporters are membrane proteins that are involved in mediating multidrug resistance (MDR). In this article, we reveal that pevonedistat is a substrate of ABCG2 which decreases the therapeutic effect of pevonedistat. The cytotoxicity of pevonedistat was significantly weakened in ABCG2-overexpressing cells, and the drug resistance can be reversed by ABCG2 inhibitors. The ATPase assay suggested that pevonedistat can stimulate ABCG2 ATPase activity in a concentration-dependent manner. Pevonedistat showed little effect on the expression level or subcellular localization of ABCG2 after 72 h treatment. Furthermore, a pevonedistat resistance cell line S1-PR was established and overexpressed ABCG2. Generally, our study provides evidence that ABCG2 can be a prominent factor leading to pevonedistat-resistance. Furthermore, ABCG2 may also be utilized as a biomarker to monitor the development of pevonedistat resistance during cancer treatment.
journal_name
Exp Cell Resjournal_title
Experimental cell researchauthors
Wei LY,Wu ZX,Yang Y,Zhao M,Ma XY,Li JS,Yang DH,Chen ZS,Fan YFdoi
10.1016/j.yexcr.2020.111858subject
Has Abstractpub_date
2020-03-15 00:00:00pages
111858issue
2eissn
0014-4827issn
1090-2422pii
S0014-4827(20)30052-5journal_volume
388pub_type
杂志文章abstract：:Mouse embryonic stem (ES) cells are isolated from the inner cell mass (ICM)/epiblast of preimplantation embryos and are widely used in cell differentiation studies. We have previously observed differences in transcript and antigen expression following differentiation of ES cells lines in vitro. We have investigated th...
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journal_title：Experimental cell research
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journal_title：Experimental cell research
pub_type： 杂志文章
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