Arbidol inhibits human esophageal squamous cell carcinoma growth in vitro and in vivo through suppressing ataxia telangiectasia and Rad3-related protein kinase
- Zhengzhou University, China
- Kyungpook National University, Republic of Korea
- China-US Hormel Cancer Institute, China
Abstract
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. Based upon a screening of drugs approved by the Food and Drug Administration, we discovered that Arbidol could effectively inhibit the proliferation of human esophageal squamous cell carcinoma 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. Phospho-proteomics experiments, in vitro kinase assays and pull-down assays were subsequently performed in order to identify the underlying growth inhibitory mechanism. We verified Arbidol is a potential ATR inhibitor via binding to ATR kinase to reduce the phosphorylation and activation of MCM2 at Ser108. Finally, we demonstrated Arbidol had the inhibitory effect of ESCC in vivo by a PDX 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.
Data availability
The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org) via the iProX partner repository with the dataset identifier PXD034944.
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Proteomics analysis report of esophageal squamous cell carcinoma treated by ArbidolProteomeXchange Consortium, PXD034944.
Article and author information
Author details
Funding
National Natural Science Foundation of China (81872335)
- Kangdong Liu
National Natural Science Youth Foundatio of China (81902486)
- Yanan Jiang
Natural Science Foundation of Henan (161100510300)
- Kangdong Liu
The Central Plains Science and Technology Innovation Leading Talents (224200510015)
- Kangdong Liu
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Compliance with Ethics RequirementsIn this study, we established an ESCC PDX model. In this model, the tumor sample from an ESCC patient was EG20 (ESCC, male, T2N0M0II, moderately differentiated, obtained from Linzhou Cancer Hospital, Henan Province, China). The patient was fully informed of the study and provided consent. This study was approved by the Ethics Committee of Zhengzhou University (ZZUHCI-2019012).
Reviewing Editor
- Wafik S El-Deiry, Brown University, United States
Publication history
- Received: September 16, 2021
- Preprint posted: February 18, 2022 (view preprint)
- Accepted: September 8, 2022
- Accepted Manuscript published: September 9, 2022 (version 1)
- Version of Record published: September 26, 2022 (version 2)
Copyright
© 2022, Yang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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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
eLife 11:e73953.
https://doi.org/10.7554/eLife.73953
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