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Bafetinib Suppresses the Transcription of PD-L1 Through c-Myc in Lung Cancer
Given the limitations of the existing antibody-based therapies, including immune-related adverse events, poor response rates, and intravenous route of dosing, small molecules inhibitors targeting PD-L1 are highly desirable. By cell-based screening, we found that tyrosine kinase inhibitor Bafetinib d...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201485/ https://www.ncbi.nlm.nih.gov/pubmed/35721177 http://dx.doi.org/10.3389/fphar.2022.897747 |
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author | Chen, Xi Du, Qianqian Guo, Hongjie He, Qiaojun Yang, Bo Ding, Ling |
author_facet | Chen, Xi Du, Qianqian Guo, Hongjie He, Qiaojun Yang, Bo Ding, Ling |
author_sort | Chen, Xi |
collection | PubMed |
description | Given the limitations of the existing antibody-based therapies, including immune-related adverse events, poor response rates, and intravenous route of dosing, small molecules inhibitors targeting PD-L1 are highly desirable. By cell-based screening, we found that tyrosine kinase inhibitor Bafetinib dramatically suppresses PD-L1 protein expression in a dose-dependent manner. In parallel, cell membrane PD-L1 is also reduced by Bafetinib. We confirm that Bafetinib doesn’t affect the protein half-life of PD-L1 but significantly inhibits the transcription of PD-L1. Among the transcription factors that regulate PD-L1 expression, c-Myc is downregulated by Bafetinib. Bafetinib caused PD-L1 inhibition is abolished when c-Myc is knocked-down. Further, we identified that Bafetinib reduced c-Myc expression because of transcription inhibition. By using the CT26 tumor model, we further confirm that Bafetinib suppressed PD-L1 expression in vivo. In conclusion, our study shows that Bafetinib inhibits the transcription of PD-L1 through transcription factor c-Myc, suggesting that Bafetinib might be a small molecule drug targeting PD-L1. |
format | Online Article Text |
id | pubmed-9201485 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92014852022-06-17 Bafetinib Suppresses the Transcription of PD-L1 Through c-Myc in Lung Cancer Chen, Xi Du, Qianqian Guo, Hongjie He, Qiaojun Yang, Bo Ding, Ling Front Pharmacol Pharmacology Given the limitations of the existing antibody-based therapies, including immune-related adverse events, poor response rates, and intravenous route of dosing, small molecules inhibitors targeting PD-L1 are highly desirable. By cell-based screening, we found that tyrosine kinase inhibitor Bafetinib dramatically suppresses PD-L1 protein expression in a dose-dependent manner. In parallel, cell membrane PD-L1 is also reduced by Bafetinib. We confirm that Bafetinib doesn’t affect the protein half-life of PD-L1 but significantly inhibits the transcription of PD-L1. Among the transcription factors that regulate PD-L1 expression, c-Myc is downregulated by Bafetinib. Bafetinib caused PD-L1 inhibition is abolished when c-Myc is knocked-down. Further, we identified that Bafetinib reduced c-Myc expression because of transcription inhibition. By using the CT26 tumor model, we further confirm that Bafetinib suppressed PD-L1 expression in vivo. In conclusion, our study shows that Bafetinib inhibits the transcription of PD-L1 through transcription factor c-Myc, suggesting that Bafetinib might be a small molecule drug targeting PD-L1. Frontiers Media S.A. 2022-06-02 /pmc/articles/PMC9201485/ /pubmed/35721177 http://dx.doi.org/10.3389/fphar.2022.897747 Text en Copyright © 2022 Chen, Du, Guo, He, Yang and Ding. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Chen, Xi Du, Qianqian Guo, Hongjie He, Qiaojun Yang, Bo Ding, Ling Bafetinib Suppresses the Transcription of PD-L1 Through c-Myc in Lung Cancer |
title | Bafetinib Suppresses the Transcription of PD-L1 Through c-Myc in Lung Cancer
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title_full | Bafetinib Suppresses the Transcription of PD-L1 Through c-Myc in Lung Cancer
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title_fullStr | Bafetinib Suppresses the Transcription of PD-L1 Through c-Myc in Lung Cancer
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title_full_unstemmed | Bafetinib Suppresses the Transcription of PD-L1 Through c-Myc in Lung Cancer
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title_short | Bafetinib Suppresses the Transcription of PD-L1 Through c-Myc in Lung Cancer
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title_sort | bafetinib suppresses the transcription of pd-l1 through c-myc in lung cancer |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201485/ https://www.ncbi.nlm.nih.gov/pubmed/35721177 http://dx.doi.org/10.3389/fphar.2022.897747 |
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