Arbidol inhibits human esophageal squamous cell carcinoma growth in vitro and in vivo through suppressing ataxia telangiectasia and Rad3-related protein kinase
- Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, China
- China-US Hormel Cancer Institute, China
- Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou University, China
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, China
- Department of Animal Science and Biotechnology, Kyungpook National University, Republic of Korea
- Cancer Chemoprevention International Collaboration Laboratory, China
Figures
Figure 1
Arbidol inhibits ESCC cell proliferation.
(a) The structure of Arbidol. (b) KYSE150, KYSE450, and shantou human embryonic esophageal (SHEE) cell viability was detected by the IN Cell Analyzer. KYSE150 and KYSE450 cells were treated with …
Figure 2 with 1 supplement
Phosphoproteomics reveals that Arbidol inhibits tumors through minichromosome maintenance-ataxia telangiectasia and Rad3-related (MCM-ATR) signal pathway.
(a) The mass spectrometry workflow of phosphorylated proteomics analysis of KYSE150 cells after 24 hr treatment with Arbidol. (b) Histogram shows the regulation of phosphorylation sites compared to …
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Figure 2—source data 1
The original data of western blot in Figure 2.
- https://cdn.elifesciences.org/articles/73953/elife-73953-fig2-data1-v2.tif
Figure 2—figure supplement 1
Arbidol did not bind directly to CDC7.
The KYSE150 cell lysate (500 μg) was incubated with sepharose 4B beads conjugated with Arbidol or sepharose 4B beads alone. Western blot analysis was used to analyze the pull-down protein.
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Figure 2—figure supplement 1—source data 1
Arbidol did not bind directly to CDC7.
- https://cdn.elifesciences.org/articles/73953/elife-73953-fig2-figsupp1-data1-v2.tif
Figure 3 with 1 supplement
Arbidol targets ataxia telangiectasia and Rad3-related (ATR) protein to affect the DNA replication pathway in ESCC.
(a) Computational docking was used to identify the binding site of Arbidol and ATR. (b-d) Arbidol directly binds to ATR. The ATR pure protein (1 μg) (b) and esophageal squamous cell carcinoma (ESCC) …
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Figure 3—source data 1
The original data of western blot in Figure 3.
- https://cdn.elifesciences.org/articles/73953/elife-73953-fig3-data1-v2.tif
Figure 3—figure supplement 1
Purified MCM2 and ATR protein.
(a) Coomassie blue-stained gel of purified minichromosome maintenance 2 (MCM2), the black arrow indicates MCM2. (b) Mutant ataxia telangiectasia and Rad3-related (ATR) protein purified by coomassie …
Figure 4 with 2 supplements
Arbidol inhibits the proliferation of ESCC cells and arrests the cell cycle in G1-phase.
(a) Gene Set Enrichment Analysis (GSEA) indicates the representation of the cell cycle pathway in both the phosphoproteomics and proteomics datasets. (b) The expression level of p-minichromosome …
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Figure 4—source data 1
The original data of western blot in Figure 4.
- https://cdn.elifesciences.org/articles/73953/elife-73953-fig4-data1-v2.tif
Figure 4—figure supplement 1
Gene set enrichment analysis (GSEA) data.
(a, b) Gene set enrichment analysis (GSEA) included the phosphoproteomics (a) and proteomics (b) datasets. The black arrow indicates minichromosome maintenance 2 (MCM2) and ataxia telangiectasia and …
Figure 4—figure supplement 2
Arbidol can not bind directly to CDK2,CDK4, CDK6 and can not decrease the levels of p-RB1 S249, S807 and T826.
(a, b, c) Arbidol did not bind directly to CDK2, CDK4, CDK6. Recombinant CDK2 protein (a) recombinant CDK4 protein (b) recombinant CDK6 protein (c) (500 μg) were incubated with sepharose 4B beads …
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Figure 4—figure supplement 2—source data 1
The original data of western Blot in Figure 4—figure supplement 2.
- https://cdn.elifesciences.org/articles/73953/elife-73953-fig4-figsupp2-data1-v2.tif
Figure 5
Knocking down of ATR reduces the growth of ESCC cells.
(a) The correlation between ataxia telangiectasia and Rad3-related (ATR) and minichromosome maintenance 2 (MCM2) was detected by gene correlation analysis. (b) The Cancer Genome Atlas data results …
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Figure 5—source data 1
The original data of western blot in Figure 5.
- https://cdn.elifesciences.org/articles/73953/elife-73953-fig5-data1-v2.tif
Figure 6
Antitumor efficacy of Arbidol in an ESCC patient-derived xenograft model.
(a) Arbidol treatment protocol for esophageal squamous cell carcinoma (ESCC) patient-derived xenograft (PDX) models. (b) Tumor sizes of the EG20 xenografts were shown. Tumors were excised and …
