Effect of Src Tyrosine Kinase Inhibition on Secretion of MMP-2 and MMP-9 by Non-small Cell Lung Cancer Cells.
Summary of "Effect of Src Tyrosine Kinase Inhibition on Secretion of MMP-2 and MMP-9 by Non-small Cell Lung Cancer Cells."
BACKGROUND:
Src tyrosine kinase and matrix metalloproteinase play the pivotal roles in lung cancer invasion and metastasis. The aim of this study is to evaluate the effect of Src tyrosine kinase inhibition on secretion of matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) by non-small cell lung cancer (NSCLC) cells.
METHODS:
ELISA was used to examine the activity of MMP-2 and MMP-9 produced by NSCLC cells (PC14PE6, H226, PC-9, A549) as well as the effect of Src tyrosine kinase inhibition on secretion of MMP-2 and MMP-9 by NSCLC cells. Boyden chamber assay was used to assess the effect of Src tyrosine kinase inhibition on invasion of NSCLC cells in vitro.
RESULTS:
The levels of MMP-2 and MMP-9 in PC14PE6 and H226 cells were high, whereas the level of MMP-9 in A549 cell was low. MMP-2 and MMP-9 levels in PC-9 cell could not be detected. Src tyrosine kinase inhibitor obviously decreased the secretion of MMP-9 by PC14PE6, H226 and A549 cells, as well as MMP-2 by PC14PE6 cells in a dose-dependent manner. 10 μM Src tyrosine kinase inhibitor suppressed the secretion of MMP-9 by H226 and A549 cells, as wells as MMP-2 by PC14PE6 cells by more than 50%, while the same concentration of Src tyrosine kinase inhibitor almost had no effect on the level of MMP-2 in H226 cell. Invasiveness of NSCLC cells was suppressed by Src tyrosine kinase inhibitor in a dose-dependent manner, though there was minor difference in degree of the inhibition among four cell lines. 3 μM Src tyrosine kinase inhibitor suppressed the cell invasiveness of PC14PE6, H226, A549 and PC-9 cells by 79.1%, 68.09%, 90.96% and 96.98%, respectively (P < 0.001).
CONCLUSIONS:
Inhibition of Src tyrosine kinase could suppress the invasion of NSCLC cells as well as the secretion of MMP-2 and MMP-9 by NSCLC cells in vitro. MMP-2 and MMP-9 were involved in regulating cell migration and invasion.
Affiliation
2nd Department of Respiratory Medicine, Shengjing Hospital of China Medical University, Shenyang 110022, China.
Journal Details
This article was published in the following journal.
Name: Zhongguo fei ai za zhi = Chinese journal of lung cancer
ISSN: 1999-6187
Pages: 13-17
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21219825
- DOI: http://dx.doi.org/10.3779/j.issn.1009-3419.2011.01.03
Medical and Biotech [MESH] Definitions
Zap-70 Protein-tyrosine Kinase
A protein tyrosine kinase that is required for T-CELL development and T-CELL ANTIGEN RECEPTOR function.
Carcinoma, Bronchogenic
Malignant neoplasm arising from the epithelium of the BRONCHI. It represents a large group of epithelial lung malignancies which can be divided into two clinical groups: SMALL CELL LUNG CANCER and NON-SMALL-CELL LUNG CARCINOMA.
Small Cell Lung Carcinoma
A form of highly malignant lung cancer that is composed of small ovoid cells (SMALL CELL CARCINOMA).
Lymphocyte Specific Protein Tyrosine Kinase P56(lck)
This enzyme is a lymphoid-specific src family tyrosine kinase that is critical for T-cell development and activation. Lck is associated with the cytoplasmic domains of CD4, CD8 and the beta-chain of the IL-2 receptor, and is thought to be involved in the earliest steps of TCR-mediated T-cell activation.
Famotidine
A competitive histamine H2-receptor antagonist. Its main pharmacodynamic effect is the inhibition of gastric secretion.
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