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FEBS Lett ; 595(5): 563-576, 2021 03.
Article in English | MEDLINE | ID: mdl-33421110

ABSTRACT

Programmed death-ligand 1 (PD-L1) is a co-inhibitory molecule expressed on tumor cells. Immune checkpoint inhibitors focusing on the PD-L1 mechanism are now being studied for the treatment of various cancer types. However, the regulatory mechanism of PD-L1 is yet to be fully clarified, and a high-throughput system for comparing the abilities of small compounds in regulating PD-L1 has not yet been established. Therefore, we created a HiBiT-tagged lung adenocarcinoma cell line, PC9-KI, for easier and faster detection of changes in PD-L1 protein expression. Using PC9-KI cells, we screened 1280 chemical compounds from the Library of Pharmacologically Active Compounds and identified microtubule polymerization inhibitors and thapsigargin as PD-L1 upregulators and a p97 inhibitor as a PD-L1 downregulator.


Subject(s)
Antineoplastic Agents/pharmacology , B7-H1 Antigen/genetics , Recombinant Fusion Proteins/genetics , Respiratory Mucosa/drug effects , Small Molecule Libraries/pharmacology , Tubulin Modulators/pharmacology , B7-H1 Antigen/agonists , B7-H1 Antigen/antagonists & inhibitors , B7-H1 Antigen/metabolism , Benzimidazoles/pharmacology , Cell Line, Tumor , Founder Effect , Gene Expression , Genes, Reporter , High-Throughput Screening Assays , Humans , Luminescent Measurements , Oligopeptides/genetics , Oligopeptides/metabolism , Protein Engineering/methods , Quinazolines/pharmacology , Recombinant Fusion Proteins/metabolism , Respiratory Mucosa/metabolism , Respiratory Mucosa/pathology , Thapsigargin/pharmacology , Valosin Containing Protein/antagonists & inhibitors , Valosin Containing Protein/genetics , Valosin Containing Protein/metabolism
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