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Effect of staurosporine on the mobility and invasiveness of lung adenocarcinoma A549 cells: an in vitro study
BACKGROUND: Lung cancer is one of the most malignant tumors, representing a significant threat to human health. Lung cancer patients often exhibit tumor cell invasion and metastasis before diagnosis which often render current treatments ineffective. Here, we investigated the effect of staurosporine,...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2702389/ https://www.ncbi.nlm.nih.gov/pubmed/19500428 http://dx.doi.org/10.1186/1471-2407-9-174 |
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author | Wang, Yanyan Yang, Hongfa Liu, Hongbin Huang, Ji Song, Xingfu |
author_facet | Wang, Yanyan Yang, Hongfa Liu, Hongbin Huang, Ji Song, Xingfu |
author_sort | Wang, Yanyan |
collection | PubMed |
description | BACKGROUND: Lung cancer is one of the most malignant tumors, representing a significant threat to human health. Lung cancer patients often exhibit tumor cell invasion and metastasis before diagnosis which often render current treatments ineffective. Here, we investigated the effect of staurosporine, a potent protein kinase C (PKC) inhibitor on the mobility and invasiveness of human lung adenocarcinoma A549 cells. METHODS: All experiments were conducted using human lung adenocarcinoma A549 cells that were either untreated or treated with 1 nmol/L, 10 nmol/L, or 100 nmol/L staurosporine. Electron microscopy analyses were performed to study ultrastructural differences between untreated A549 cells and A549 cells treated with staurosporine. The effect of staurosporine on the mobility and invasiveness of A549 was tested using Transwell chambers. Western blot analyses were performed to study the effect of staurosporine on the levels of PKC-α, integrin β1, E-cadherin, and LnR. Changes in MMP-9 and uPA levels were identified by fluorescence microscopy. RESULTS: We demonstrated that treatment of A549 cells with staurosporine caused alterations in the cell shape and morphology. Untreated cells were primarily short spindle- and triangle-shaped in contrast to staurosporine treated cells which were retracted and round-shaped. The latter showed signs of apoptosis, including vacuole fragmentation, chromatin degeneration, and a decrease in the number of microvilli at the surface of the cells. The A549 cell adhesion, mobility, and invasiveness significantly decreased with higher staurosporine concentrations. E-cadherin, integrin β1, and LnR levels changed by a factor of 1.5, 0.74, and 0.73, respectively compared to untreated cells. In addition, the levels of MMP-9 and uPA decreased in cells treated with staurosporine. CONCLUSION: In summary, this study demonstrates that staurosporine inhibits cell adhesion, mobility, and invasion of A549 cells. The staurosporine-mediated inhibition of PKC-α, induction of E-Cad expression, and decreased integrin β1, LnR, MMP-9, and uPA levels could all possibly contribute to this biological process. These results represent a significant step forward in the ongoing effort to understand the development of lung carcinoma and to design novel strategies to inhibit metastasis of the tumor by targeting the cell-adhesion, mobility and invasion of tumor cells. |
format | Text |
id | pubmed-2702389 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-27023892009-06-27 Effect of staurosporine on the mobility and invasiveness of lung adenocarcinoma A549 cells: an in vitro study Wang, Yanyan Yang, Hongfa Liu, Hongbin Huang, Ji Song, Xingfu BMC Cancer Research Article BACKGROUND: Lung cancer is one of the most malignant tumors, representing a significant threat to human health. Lung cancer patients often exhibit tumor cell invasion and metastasis before diagnosis which often render current treatments ineffective. Here, we investigated the effect of staurosporine, a potent protein kinase C (PKC) inhibitor on the mobility and invasiveness of human lung adenocarcinoma A549 cells. METHODS: All experiments were conducted using human lung adenocarcinoma A549 cells that were either untreated or treated with 1 nmol/L, 10 nmol/L, or 100 nmol/L staurosporine. Electron microscopy analyses were performed to study ultrastructural differences between untreated A549 cells and A549 cells treated with staurosporine. The effect of staurosporine on the mobility and invasiveness of A549 was tested using Transwell chambers. Western blot analyses were performed to study the effect of staurosporine on the levels of PKC-α, integrin β1, E-cadherin, and LnR. Changes in MMP-9 and uPA levels were identified by fluorescence microscopy. RESULTS: We demonstrated that treatment of A549 cells with staurosporine caused alterations in the cell shape and morphology. Untreated cells were primarily short spindle- and triangle-shaped in contrast to staurosporine treated cells which were retracted and round-shaped. The latter showed signs of apoptosis, including vacuole fragmentation, chromatin degeneration, and a decrease in the number of microvilli at the surface of the cells. The A549 cell adhesion, mobility, and invasiveness significantly decreased with higher staurosporine concentrations. E-cadherin, integrin β1, and LnR levels changed by a factor of 1.5, 0.74, and 0.73, respectively compared to untreated cells. In addition, the levels of MMP-9 and uPA decreased in cells treated with staurosporine. CONCLUSION: In summary, this study demonstrates that staurosporine inhibits cell adhesion, mobility, and invasion of A549 cells. The staurosporine-mediated inhibition of PKC-α, induction of E-Cad expression, and decreased integrin β1, LnR, MMP-9, and uPA levels could all possibly contribute to this biological process. These results represent a significant step forward in the ongoing effort to understand the development of lung carcinoma and to design novel strategies to inhibit metastasis of the tumor by targeting the cell-adhesion, mobility and invasion of tumor cells. BioMed Central 2009-06-08 /pmc/articles/PMC2702389/ /pubmed/19500428 http://dx.doi.org/10.1186/1471-2407-9-174 Text en Copyright ©2009 Wang et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Wang, Yanyan Yang, Hongfa Liu, Hongbin Huang, Ji Song, Xingfu Effect of staurosporine on the mobility and invasiveness of lung adenocarcinoma A549 cells: an in vitro study |
title | Effect of staurosporine on the mobility and invasiveness of lung adenocarcinoma A549 cells: an in vitro study |
title_full | Effect of staurosporine on the mobility and invasiveness of lung adenocarcinoma A549 cells: an in vitro study |
title_fullStr | Effect of staurosporine on the mobility and invasiveness of lung adenocarcinoma A549 cells: an in vitro study |
title_full_unstemmed | Effect of staurosporine on the mobility and invasiveness of lung adenocarcinoma A549 cells: an in vitro study |
title_short | Effect of staurosporine on the mobility and invasiveness of lung adenocarcinoma A549 cells: an in vitro study |
title_sort | effect of staurosporine on the mobility and invasiveness of lung adenocarcinoma a549 cells: an in vitro study |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2702389/ https://www.ncbi.nlm.nih.gov/pubmed/19500428 http://dx.doi.org/10.1186/1471-2407-9-174 |
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