DS-1 Inhibits Migration and Invasion of Non-small-cell Lung Cancer Cells Through Suppression of Epithelial to Mesenchymal Transition and Integrin β1/FAK Signaling.
Carcinoma, Non-Small-Cell Lung
/ pathology
Cell Line, Tumor
Cell Proliferation
/ drug effects
Epithelial-Mesenchymal Transition
/ drug effects
Focal Adhesion Protein-Tyrosine Kinases
/ antagonists & inhibitors
Humans
Integrin beta1
/ drug effects
Lung Neoplasms
/ pathology
Signal Transduction
/ drug effects
DS-1
EMT
FAK
integrin
non-small cell lung cancer
Journal
Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988
Informations de publication
Date de publication:
Jun 2021
Jun 2021
Historique:
received:
01
04
2021
revised:
16
04
2021
accepted:
28
04
2021
entrez:
4
6
2021
pubmed:
5
6
2021
medline:
22
6
2021
Statut:
ppublish
Résumé
Epithelial to mesenchymal transition (EMT), and focal adhesion kinase (FAK) facilitate lung cancer cell motility and survival. We, therefore, investigated the antimigratory effect of 3,4-dihydroxy-5,4'-dimethoxybibenzyl (DS-1) on human lung cancer cells. Cell viability and proliferation were examined by the 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide assay. Filopodia formation, migration, and anchorage-independent growth assays were performed to assess metastatic behaviors while EMT-related proteins, integrins, and FAK-RhoA pathway were evaluated by western blot analysis. We found that DS-1 significantly inhibited the proliferation of lung cancer cells compared to the control. The aggressive behavior of cancer cells, including migration and invasion, was significantly reduced by DS-1. Anchorage-independent growth analysis provided evidence that DS-1 suppressed the growth and survival of cancer cells in detached conditions as indicated by the significant reduction in size and number of colonies. With regard to the mechanisms involved, we found that DS-1-suppressed EMT, as indicated by the reduction of EMT markers, namely N-cadherin, SNAIL and SLUG, and increased levels of the epithelial marker, E-cadherin. In addition, DS-1 was shown to reduce the level of integrin β1 protein and FAK activation. DS-1 suppressed lung cancer metastasis via suppressing EMT, integrin β1 expression and FAK-related signaling.
Sections du résumé
BACKGROUND/AIM
OBJECTIVE
Epithelial to mesenchymal transition (EMT), and focal adhesion kinase (FAK) facilitate lung cancer cell motility and survival. We, therefore, investigated the antimigratory effect of 3,4-dihydroxy-5,4'-dimethoxybibenzyl (DS-1) on human lung cancer cells.
MATERIALS AND METHODS
METHODS
Cell viability and proliferation were examined by the 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide assay. Filopodia formation, migration, and anchorage-independent growth assays were performed to assess metastatic behaviors while EMT-related proteins, integrins, and FAK-RhoA pathway were evaluated by western blot analysis.
RESULTS
RESULTS
We found that DS-1 significantly inhibited the proliferation of lung cancer cells compared to the control. The aggressive behavior of cancer cells, including migration and invasion, was significantly reduced by DS-1. Anchorage-independent growth analysis provided evidence that DS-1 suppressed the growth and survival of cancer cells in detached conditions as indicated by the significant reduction in size and number of colonies. With regard to the mechanisms involved, we found that DS-1-suppressed EMT, as indicated by the reduction of EMT markers, namely N-cadherin, SNAIL and SLUG, and increased levels of the epithelial marker, E-cadherin. In addition, DS-1 was shown to reduce the level of integrin β1 protein and FAK activation.
CONCLUSION
CONCLUSIONS
DS-1 suppressed lung cancer metastasis via suppressing EMT, integrin β1 expression and FAK-related signaling.
Identifiants
pubmed: 34083282
pii: 41/6/2913
doi: 10.21873/anticanres.15073
doi:
Substances chimiques
Integrin beta1
0
Focal Adhesion Protein-Tyrosine Kinases
EC 2.7.10.2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2913-2923Informations de copyright
Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.