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Arbidol inhibits human esophageal squamous cell carcinoma growth in vitro and in vivo through suppressing ataxia telangiectasia and Rad3-related protein kinase

Human esophageal cancer has a global impact on human health due to its high incidence and mortality. Therefore, there is an urgent need to develop new drugs to treat or prevent the prominent pathological subtype of esophageal cancer, esophageal squamous cell carcinoma (ESCC). Based upon the screenin...

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Autores principales: Yang, Ning, Lu, Xuebo, Jiang, Yanan, Zhao, Lili, Wang, Donghao, Wei, Yaxing, Yu, Yin, Kim, Myoung Ok, Laster, Kyle Vaughn, Li, Xin, Yuan, Baoyin, Dong, Zigang, Liu, Kangdong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9512399/
https://www.ncbi.nlm.nih.gov/pubmed/36082941
http://dx.doi.org/10.7554/eLife.73953
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author Yang, Ning
Lu, Xuebo
Jiang, Yanan
Zhao, Lili
Wang, Donghao
Wei, Yaxing
Yu, Yin
Kim, Myoung Ok
Laster, Kyle Vaughn
Li, Xin
Yuan, Baoyin
Dong, Zigang
Liu, Kangdong
author_facet Yang, Ning
Lu, Xuebo
Jiang, Yanan
Zhao, Lili
Wang, Donghao
Wei, Yaxing
Yu, Yin
Kim, Myoung Ok
Laster, Kyle Vaughn
Li, Xin
Yuan, Baoyin
Dong, Zigang
Liu, Kangdong
author_sort Yang, Ning
collection PubMed
description Human esophageal cancer has a global impact on human health due to its high incidence and mortality. Therefore, there is an urgent need to develop new drugs to treat or prevent the prominent pathological subtype of esophageal cancer, esophageal squamous cell carcinoma (ESCC). Based upon the screening of drugs approved by the Food and Drug Administration, we discovered that Arbidol could effectively inhibit the proliferation of human ESCC in vitro. Next, we conducted a series of cell-based assays and found that Arbidol treatment inhibited the proliferation and colony formation ability of ESCC cells and promoted G1-phase cell cycle arrest. Phosphoproteomics experiments, in vitro kinase assays and pull-down assays were subsequently performed in order to identify the underlying growth inhibitory mechanism. We verified that Arbidol is a potential ataxia telangiectasia and Rad3-related (ATR) inhibitor via binding to ATR kinase to reduce the phosphorylation and activation of minichromosome maintenance protein 2 at Ser108. Finally, we demonstrated Arbidol had the inhibitory effect of ESCC in vivo by a patient-derived xenograft model. All together, Arbidol inhibits the proliferation of ESCC in vitro and in vivo through the DNA replication pathway and is associated with the cell cycle.
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spelling pubmed-95123992022-09-27 Arbidol inhibits human esophageal squamous cell carcinoma growth in vitro and in vivo through suppressing ataxia telangiectasia and Rad3-related protein kinase Yang, Ning Lu, Xuebo Jiang, Yanan Zhao, Lili Wang, Donghao Wei, Yaxing Yu, Yin Kim, Myoung Ok Laster, Kyle Vaughn Li, Xin Yuan, Baoyin Dong, Zigang Liu, Kangdong eLife Cancer Biology Human esophageal cancer has a global impact on human health due to its high incidence and mortality. Therefore, there is an urgent need to develop new drugs to treat or prevent the prominent pathological subtype of esophageal cancer, esophageal squamous cell carcinoma (ESCC). Based upon the screening of drugs approved by the Food and Drug Administration, we discovered that Arbidol could effectively inhibit the proliferation of human ESCC in vitro. Next, we conducted a series of cell-based assays and found that Arbidol treatment inhibited the proliferation and colony formation ability of ESCC cells and promoted G1-phase cell cycle arrest. Phosphoproteomics experiments, in vitro kinase assays and pull-down assays were subsequently performed in order to identify the underlying growth inhibitory mechanism. We verified that Arbidol is a potential ataxia telangiectasia and Rad3-related (ATR) inhibitor via binding to ATR kinase to reduce the phosphorylation and activation of minichromosome maintenance protein 2 at Ser108. Finally, we demonstrated Arbidol had the inhibitory effect of ESCC in vivo by a patient-derived xenograft model. All together, Arbidol inhibits the proliferation of ESCC in vitro and in vivo through the DNA replication pathway and is associated with the cell cycle. eLife Sciences Publications, Ltd 2022-09-09 /pmc/articles/PMC9512399/ /pubmed/36082941 http://dx.doi.org/10.7554/eLife.73953 Text en © 2022, Yang, Lu, Jiang et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cancer Biology
Yang, Ning
Lu, Xuebo
Jiang, Yanan
Zhao, Lili
Wang, Donghao
Wei, Yaxing
Yu, Yin
Kim, Myoung Ok
Laster, Kyle Vaughn
Li, Xin
Yuan, Baoyin
Dong, Zigang
Liu, Kangdong
Arbidol inhibits human esophageal squamous cell carcinoma growth in vitro and in vivo through suppressing ataxia telangiectasia and Rad3-related protein kinase
title Arbidol inhibits human esophageal squamous cell carcinoma growth in vitro and in vivo through suppressing ataxia telangiectasia and Rad3-related protein kinase
title_full Arbidol inhibits human esophageal squamous cell carcinoma growth in vitro and in vivo through suppressing ataxia telangiectasia and Rad3-related protein kinase
title_fullStr Arbidol inhibits human esophageal squamous cell carcinoma growth in vitro and in vivo through suppressing ataxia telangiectasia and Rad3-related protein kinase
title_full_unstemmed Arbidol inhibits human esophageal squamous cell carcinoma growth in vitro and in vivo through suppressing ataxia telangiectasia and Rad3-related protein kinase
title_short Arbidol inhibits human esophageal squamous cell carcinoma growth in vitro and in vivo through suppressing ataxia telangiectasia and Rad3-related protein kinase
title_sort arbidol inhibits human esophageal squamous cell carcinoma growth in vitro and in vivo through suppressing ataxia telangiectasia and rad3-related protein kinase
topic Cancer Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9512399/
https://www.ncbi.nlm.nih.gov/pubmed/36082941
http://dx.doi.org/10.7554/eLife.73953
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