A novel nanobody as therapeutics target for EGFR-positive colorectal cancer therapy: exploring the effects of the nanobody on SW480 cells using proteomics approach.

Antibodies Gefitinib LC–MS/MS Protein interactions SW480 Tyrosine kinase inhibitors

Journal

Proteome science
ISSN: 1477-5956
Titre abrégé: Proteome Sci
Pays: England
ID NLM: 101170539

Informations de publication

Date de publication:
16 May 2022
Historique:
received: 15 01 2022
accepted: 24 04 2022
entrez: 16 5 2022
pubmed: 17 5 2022
medline: 17 5 2022
Statut: epublish

Résumé

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. 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 . The half-maximal inhibitory concentration (IC 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.

Sections du résumé

BACKGROUND 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 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 RESULTS
The half-maximal inhibitory concentration (IC
CONCLUSION CONCLUSIONS
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.

Identifiants

pubmed: 35578244
doi: 10.1186/s12953-022-00190-6
pii: 10.1186/s12953-022-00190-6
pmc: PMC9109347
doi:

Types de publication

Journal Article

Langues

eng

Pagination

9

Subventions

Organisme : Royal Golden Jubilee (RGJ) Ph.D. Programme
ID : PHD/0152/2557
Organisme : Royal Golden Jubilee (RGJ) Ph.D. Programme
ID : PHD/0152/2557

Informations de copyright

© 2022. The Author(s).

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Auteurs

Thomanai Lamtha (T)

Department of Biochemistry, Faculty of Science, Laboratory of Protein Engineering and Bioinformatics, Kasetsart University, Ngam Wong Wan, Chatuchak, Bangkok, 10900, Thailand.

Sucheewin Krobthong (S)

Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand.
Center for Neuroscience, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand.

Yodying Yingchutrakul (Y)

Center for Neuroscience, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand.
National Omics Center, NSTDA, Pathum Thani, 12120, Thailand.

Pawitrabhorn Samutrtai (P)

Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, 50200, Thailand.

Christopher Gerner (C)

Department of Analytical Chemistry, University of Vienna, Währinger Straße 38, 1090, Vienna, Austria.

Lueacha Tabtimmai (L)

Department of Biotechnology, Faculty of Applied Science, King Mongkut's University of Technology North Bangkok, Bangkok, 10800, Thailand.

Kiattawee Choowongkomon (K)

Department of Biochemistry, Faculty of Science, Laboratory of Protein Engineering and Bioinformatics, Kasetsart University, Ngam Wong Wan, Chatuchak, Bangkok, 10900, Thailand. kiattawee.c@ku.th.

Classifications MeSH