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A novel nanobody as therapeutics target for EGFR-positive colorectal cancer therapy: exploring the effects of the nanobody on SW480 cells using proteomics approach
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Document Title
A novel nanobody as therapeutics target for EGFR-positive colorectal cancer therapy: exploring the effects of the nanobody on SW480 cells using proteomics approach
Author
Lamtha T., Krobthong S., Yingchutrakul Y., Samutrtai P., Gerner C., Tabtimmai L., Choowongkomon K.,
Name from Authors Collection
Scopus Author ID
57434422300
Scopus Author ID
7003781554
Affiliations
Department of Biochemistry, Faculty of Science, Laboratory of Protein Engineering and Bioinformatics, Kasetsart University, Ngam Wong Wan, Chatuchak, Bangkok, 10900, Thailand; Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand; Center for Neuroscience, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand; National Omics Center, NSTDA, Pathum Thani, 12120, Thailand; Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, 50200, Thailand; Department of Analytical Chemistry, University of Vienna, Währinger Straße 38, Vienna, 1090, Austria; Department of Biotechnology, Faculty of Applied Science, King Mongkut’s University of Technology North Bangkok, Bangkok, 10800, Thailand
Type
Article
Source Title
Proteome Science
ISSN
14775956
Year
2022
Volume
20
Issue
1
Open Access
Gold, Green
Publisher
BioMed Central Ltd
DOI
10.1186/s12953-022-00190-6
Format
Abstract
Background: The epidermal growth factor receptor (EGFR) overexpression is found in metastatic colorectal cancer (mCRC). Targeted molecular therapies such as monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKI) are becoming more precise, targeting specifically for cancer therapeutics. However, there are adverse effects of currently available anti-EGFR drugs, including drug-resistant and side effects. Nanobodies can overcome these limitations. Our previous study has found that cell-penetrable nanobodies targeted at EGFR-tyrosine kinase were significantly reduced EGFR-positive lung cancer cells viability and proliferation. The aim of the present study was to determine the effect of cell-penetrable nanobody (R9VH36) on cell viability and proteomic profile in EGFR-positive human colorectal cancer cell lines. Methods: The human colorectal carcinoma cell line (SW480) was treated with R9VH36, compared with gefitinib. Cell viability was monitored using the MTT cell viability assay. The proteomic profiling was analyzed by LC–MS/MS. Results: The half-maximal inhibitory concentration (IC50) values determined for R9VH36 and gefitinib against SW480 were 527 ± 0.03 nM and 13.31 ± 0.02 μM, respectively. Moreover, both the gefitinib-treated group and nanobody-treated group had completely different proteome profiles. A total 6626 differentially expressed proteins were identified. PCA analysis revealed different proteome profiling in R9VH36 experiment. There were 8 proteins in R9VH36 that significantly exhibited opposite expression directions when compared to gefitinib. These proteins are involved in DNA-damage checkpoint processes. Conclusion: The proteomics explored those 6,626 proteins had different expressions between R9VH36 and gefitinib. There were 8 proteins in R9VH36 exhibited opposite expression direction when comparing to gefitinib. Our findings suggest that R9VH36 has the potential to be an alternative remedy for treating EGFR-positive colon cancer. © 2022, The Author(s).
Keyword
Antibodies | Article | cancer immunotherapy | cell viability | colorectal cancer | controlled study | DNA damage | drug targeting | epidermal growth factor receptor | Gefitinib | Human | human cell | IC50 | LC–MS/MS | Liquid chromatography-mass spectrometry | nanobody | protein analysis | protein expression | Protein interactions | Proteomics | SW480 | SW480 cell line | Tyrosine kinase inhibitors
Industrial Classification
Knowledge Taxonomy Level 1
Knowledge Taxonomy Level 2
Funding Sponsor
Kasetsart University Research and Development Institute CC BY Author
License
CC BY
Rights
Author
Publication Source
Scopus