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Small interference RNA targeting tissue factor inhibits human lung adenocarcinoma growth in vitro and in vivo
BACKGROUND: The human coagulation trigger tissue factor (TF) is overexpressed in several types of cancer and involved in tumor growth, vascularization, and metastasis. To explore the role of TF in biological processes of lung adenocarcinoma, we used RNA interference (RNAi) technology to silence TF i...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3118969/ https://www.ncbi.nlm.nih.gov/pubmed/21619686 http://dx.doi.org/10.1186/1756-9966-30-63 |
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author | Xu, Chengcheng Gui, Qi Chen, Wenshu Wu, Leiming Sun, Wei Zhang, Ni Xu, Qinzi Wang, Jianing Fu, Xiangning |
author_facet | Xu, Chengcheng Gui, Qi Chen, Wenshu Wu, Leiming Sun, Wei Zhang, Ni Xu, Qinzi Wang, Jianing Fu, Xiangning |
author_sort | Xu, Chengcheng |
collection | PubMed |
description | BACKGROUND: The human coagulation trigger tissue factor (TF) is overexpressed in several types of cancer and involved in tumor growth, vascularization, and metastasis. To explore the role of TF in biological processes of lung adenocarcinoma, we used RNA interference (RNAi) technology to silence TF in a lung adenocarcinoma cell line A549 with high-level expression of TF and evaluate its antitumor effects in vitro and in vivo. METHODS: The specific small interfering RNA (siRNA) designed for targeting human TF was transfected into A549 cells. The expression of TF was detected by reverse transcription-PCR and Western blot. Cell proliferation was measured by MTT and clonogenic assays. Cell apoptosis was assessed by flow cytometry. The metastatic potential of A549 cells was determined by wound healing, the mobility and Matrigel invasion assays. Expressions of PI3K/Akt, Erk1/2, VEGF and MMP-2/-9 in transfected cells were detected by Western blot. In vivo, the effect of TF-siRNA on the growth of A549 lung adenocarcinoma xenografts in nude mice was investigated. RESULTS: TF -siRNA significantly reduced the expression of TF in the mRNA and protein levels. The down-regulation of TF in A549 cells resulted in the suppression of cell proliferation, invasion and metastasis and induced cell apoptosis in dose-dependent manner. Erk MAPK, PI3K/Akt pathways as well as VEGF and MMP-2/-9 expressions were inhibited in TF-siRNA transfected cells. Moreover, intratumoral injection of siRNA targeting TF suppressed the tumor growth of A549 cells in vivo model of lung adenocarcinoma. CONCLUSIONS: Down-regulation of TF using siRNA could provide a potential approach for gene therapy against lung adenocarcinoma, and the antitumor effects may be associated with inhibition of Erk MAPK, PI3K/Akt pathways. |
format | Online Article Text |
id | pubmed-3118969 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-31189692011-06-22 Small interference RNA targeting tissue factor inhibits human lung adenocarcinoma growth in vitro and in vivo Xu, Chengcheng Gui, Qi Chen, Wenshu Wu, Leiming Sun, Wei Zhang, Ni Xu, Qinzi Wang, Jianing Fu, Xiangning J Exp Clin Cancer Res Research BACKGROUND: The human coagulation trigger tissue factor (TF) is overexpressed in several types of cancer and involved in tumor growth, vascularization, and metastasis. To explore the role of TF in biological processes of lung adenocarcinoma, we used RNA interference (RNAi) technology to silence TF in a lung adenocarcinoma cell line A549 with high-level expression of TF and evaluate its antitumor effects in vitro and in vivo. METHODS: The specific small interfering RNA (siRNA) designed for targeting human TF was transfected into A549 cells. The expression of TF was detected by reverse transcription-PCR and Western blot. Cell proliferation was measured by MTT and clonogenic assays. Cell apoptosis was assessed by flow cytometry. The metastatic potential of A549 cells was determined by wound healing, the mobility and Matrigel invasion assays. Expressions of PI3K/Akt, Erk1/2, VEGF and MMP-2/-9 in transfected cells were detected by Western blot. In vivo, the effect of TF-siRNA on the growth of A549 lung adenocarcinoma xenografts in nude mice was investigated. RESULTS: TF -siRNA significantly reduced the expression of TF in the mRNA and protein levels. The down-regulation of TF in A549 cells resulted in the suppression of cell proliferation, invasion and metastasis and induced cell apoptosis in dose-dependent manner. Erk MAPK, PI3K/Akt pathways as well as VEGF and MMP-2/-9 expressions were inhibited in TF-siRNA transfected cells. Moreover, intratumoral injection of siRNA targeting TF suppressed the tumor growth of A549 cells in vivo model of lung adenocarcinoma. CONCLUSIONS: Down-regulation of TF using siRNA could provide a potential approach for gene therapy against lung adenocarcinoma, and the antitumor effects may be associated with inhibition of Erk MAPK, PI3K/Akt pathways. BioMed Central 2011-05-28 /pmc/articles/PMC3118969/ /pubmed/21619686 http://dx.doi.org/10.1186/1756-9966-30-63 Text en Copyright ©2011 Xu 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 Xu, Chengcheng Gui, Qi Chen, Wenshu Wu, Leiming Sun, Wei Zhang, Ni Xu, Qinzi Wang, Jianing Fu, Xiangning Small interference RNA targeting tissue factor inhibits human lung adenocarcinoma growth in vitro and in vivo |
title | Small interference RNA targeting tissue factor inhibits human lung adenocarcinoma growth in vitro and in vivo |
title_full | Small interference RNA targeting tissue factor inhibits human lung adenocarcinoma growth in vitro and in vivo |
title_fullStr | Small interference RNA targeting tissue factor inhibits human lung adenocarcinoma growth in vitro and in vivo |
title_full_unstemmed | Small interference RNA targeting tissue factor inhibits human lung adenocarcinoma growth in vitro and in vivo |
title_short | Small interference RNA targeting tissue factor inhibits human lung adenocarcinoma growth in vitro and in vivo |
title_sort | small interference rna targeting tissue factor inhibits human lung adenocarcinoma growth in vitro and in vivo |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3118969/ https://www.ncbi.nlm.nih.gov/pubmed/21619686 http://dx.doi.org/10.1186/1756-9966-30-63 |
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