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Recombinant Human Endostatin Endostar Suppresses Angiogenesis and Lymphangiogenesis of Malignant Pleural Effusion in Mice

Identifieur interne : 004462 ( Pmc/Curation ); précédent : 004461; suivant : 004463

Recombinant Human Endostatin Endostar Suppresses Angiogenesis and Lymphangiogenesis of Malignant Pleural Effusion in Mice

Auteurs : Xingqun Ma [République populaire de Chine] ; Yanwen Yao [République populaire de Chine] ; Dongmei Yuan [République populaire de Chine] ; Hongbing Liu [République populaire de Chine] ; Shouju Wang [République populaire de Chine] ; Changsheng Zhou [République populaire de Chine] ; Yong Song [République populaire de Chine]

Source :

RBID : PMC:3532165

Abstract

Background

Malignant pleural effusion (MPE) is a common complication of lung cancer. One widely used treatment for MPE is Endostar, a recombined humanized endostatin based treatment. However, the mechanism of this treatment is still unclear. The aim of this study was to investigate the effects of Endostar in mice with MPE.

Methods and Materials

Lewis lung carcinoma (LLC) cell line expressing enhanced green fluorescent protein (EGFP) was injected into pleural cavity to establish MPE mice model. Mice were randomly divided into four groups. High dose of Endostar (30 mg/kg), low dose of Endostar (8 mg/kg), normal saline, or Bevacizumab (5 mg/kg) was respectively injected into pleural cavity three times with 3-day interval in each group. Transverse computed tomography (CT) was performed to observe pleural fluid formation 14 days after LLC cells injection. Mice were anesthetized and sacrificed 3 days after final administration. The volume of pleural effusion n was measured using 1 ml syringe. Micro blood vessel density (MVD), Lymphatic micro vessel density (LMVD), the expression level of vascular endothelial growth factor A (VEGF-A) and VEGF-C were observed by immunohistochemistry (IHC) staining.

Results

The volume of pleural effusion as well as the number of pleural tumor foci, MVD and the expression of VEGF-A were significantly reduced in high dose of Endostar treat group. More importantly, LMVD and the expression of VEGF-C were markedly lower in treat group than those in the other three control groups.

Conclusion

Our work demonstrated that Endostar played an efficient anti-cancer role in MPE through its suppressive effect on angiogenesis and lymphangiogenesis, which provided a certain theoretical basis for the effectiveness of Endostar on the MPE treatment.


Url:
DOI: 10.1371/journal.pone.0053449
PubMed: 23285296
PubMed Central: 3532165

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PMC:3532165

Le document en format XML

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<p>Malignant pleural effusion (MPE) is a common complication of lung cancer. One widely used treatment for MPE is Endostar, a recombined humanized endostatin based treatment. However, the mechanism of this treatment is still unclear. The aim of this study was to investigate the effects of Endostar in mice with MPE.</p>
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<p>Lewis lung carcinoma (LLC) cell line expressing enhanced green fluorescent protein (EGFP) was injected into pleural cavity to establish MPE mice model. Mice were randomly divided into four groups. High dose of Endostar (30 mg/kg), low dose of Endostar (8 mg/kg), normal saline, or Bevacizumab (5 mg/kg) was respectively injected into pleural cavity three times with 3-day interval in each group. Transverse computed tomography (CT) was performed to observe pleural fluid formation 14 days after LLC cells injection. Mice were anesthetized and sacrificed 3 days after final administration. The volume of pleural effusion n was measured using 1 ml syringe. Micro blood vessel density (MVD), Lymphatic micro vessel density (LMVD), the expression level of vascular endothelial growth factor A (VEGF-A) and VEGF-C were observed by immunohistochemistry (IHC) staining.</p>
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<p>The volume of pleural effusion as well as the number of pleural tumor foci, MVD and the expression of VEGF-A were significantly reduced in high dose of Endostar treat group. More importantly, LMVD and the expression of VEGF-C were markedly lower in treat group than those in the other three control groups.</p>
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<p>Our work demonstrated that Endostar played an efficient anti-cancer role in MPE through its suppressive effect on angiogenesis and lymphangiogenesis, which provided a certain theoretical basis for the effectiveness of Endostar on the MPE treatment.</p>
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<pmc article-type="research-article">
<pmc-dir>properties open_access</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">PLoS One</journal-id>
<journal-id journal-id-type="iso-abbrev">PLoS ONE</journal-id>
<journal-id journal-id-type="publisher-id">plos</journal-id>
<journal-id journal-id-type="pmc">plosone</journal-id>
<journal-title-group>
<journal-title>PLoS ONE</journal-title>
</journal-title-group>
<issn pub-type="epub">1932-6203</issn>
<publisher>
<publisher-name>Public Library of Science</publisher-name>
<publisher-loc>San Francisco, USA</publisher-loc>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">23285296</article-id>
<article-id pub-id-type="pmc">3532165</article-id>
<article-id pub-id-type="publisher-id">PONE-D-12-24534</article-id>
<article-id pub-id-type="doi">10.1371/journal.pone.0053449</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Research Article</subject>
</subj-group>
<subj-group subj-group-type="Discipline-v2">
<subject>Biology</subject>
<subj-group>
<subject>Anatomy and Physiology</subject>
<subj-group>
<subject>Endocrine System</subject>
<subj-group>
<subject>Endocrine Physiology</subject>
<subj-group>
<subject>Epidermal Growth Factor</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group>
<subject>Model Organisms</subject>
<subj-group>
<subject>Animal Models</subject>
<subj-group>
<subject>Mouse</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v2">
<subject>Medicine</subject>
<subj-group>
<subject>Anatomy and Physiology</subject>
<subj-group>
<subject>Endocrine System</subject>
<subj-group>
<subject>Endocrine Physiology</subject>
<subj-group>
<subject>Epidermal Growth Factor</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group>
<subject>Clinical Research Design</subject>
<subj-group>
<subject>Animal Models of Disease</subject>
</subj-group>
</subj-group>
<subj-group>
<subject>Endocrinology</subject>
<subj-group>
<subject>Endocrine Physiology</subject>
<subj-group>
<subject>Epidermal Growth Factor</subject>
</subj-group>
</subj-group>
</subj-group>
<subj-group>
<subject>Oncology</subject>
<subj-group>
<subject>Cancer Treatment</subject>
<subj-group>
<subject>Antiangiogenesis Therapy</subject>
</subj-group>
</subj-group>
<subj-group>
<subject>Cancers and Neoplasms</subject>
<subj-group>
<subject>Lung and Intrathoracic Tumors</subject>
</subj-group>
</subj-group>
<subj-group>
<subject>Basic Cancer Research</subject>
</subj-group>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Recombinant Human Endostatin Endostar Suppresses Angiogenesis and Lymphangiogenesis of Malignant Pleural Effusion in Mice</article-title>
<alt-title alt-title-type="running-head">Endostar Suppresses Lymphangiogenesis of MPE</alt-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" equal-contrib="yes">
<name>
<surname>Ma</surname>
<given-names>Xingqun</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author" equal-contrib="yes">
<name>
<surname>Yao</surname>
<given-names>Yanwen</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Yuan</surname>
<given-names>Dongmei</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Liu</surname>
<given-names>Hongbing</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Wang</surname>
<given-names>Shouju</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Zhou</surname>
<given-names>Changsheng</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Song</surname>
<given-names>Yong</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="corresp" rid="cor1">
<sup>*</sup>
</xref>
</contrib>
</contrib-group>
<aff id="aff1">
<label>1</label>
<addr-line>Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China</addr-line>
</aff>
<aff id="aff2">
<label>2</label>
<addr-line>Department of Medical Imaging, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China</addr-line>
</aff>
<contrib-group>
<contrib contrib-type="editor">
<name>
<surname>Kalinichenko</surname>
<given-names>Vladimir V.</given-names>
</name>
<role>Editor</role>
<xref ref-type="aff" rid="edit1"></xref>
</contrib>
</contrib-group>
<aff id="edit1">
<addr-line>Cincinnati Children's Hospital Medical Center, United States of America</addr-line>
</aff>
<author-notes>
<corresp id="cor1">* E-mail:
<email>yong_song6310@yahoo.com</email>
</corresp>
<fn fn-type="conflict">
<p>
<bold>Competing Interests: </bold>
The authors have declared that no competing interests exist.</p>
</fn>
<fn fn-type="con">
<p>Conceived and designed the experiments: XQM YS. Performed the experiments: XQM SJW CSZ. Analyzed the data: XQM YWY. Contributed reagents/materials/analysis tools: XQM DMY HBL. Wrote the paper: XQM YWY YS.</p>
</fn>
</author-notes>
<pub-date pub-type="collection">
<year>2012</year>
</pub-date>
<pub-date pub-type="epub">
<day>28</day>
<month>12</month>
<year>2012</year>
</pub-date>
<volume>7</volume>
<issue>12</issue>
<elocation-id>e53449</elocation-id>
<history>
<date date-type="received">
<day>9</day>
<month>8</month>
<year>2012</year>
</date>
<date date-type="accepted">
<day>28</day>
<month>11</month>
<year>2012</year>
</date>
</history>
<permissions>
<copyright-year>2012</copyright-year>
<copyright-holder>Ma et al</copyright-holder>
<license>
<license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p>
</license>
</permissions>
<abstract>
<sec>
<title>Background</title>
<p>Malignant pleural effusion (MPE) is a common complication of lung cancer. One widely used treatment for MPE is Endostar, a recombined humanized endostatin based treatment. However, the mechanism of this treatment is still unclear. The aim of this study was to investigate the effects of Endostar in mice with MPE.</p>
</sec>
<sec>
<title>Methods and Materials</title>
<p>Lewis lung carcinoma (LLC) cell line expressing enhanced green fluorescent protein (EGFP) was injected into pleural cavity to establish MPE mice model. Mice were randomly divided into four groups. High dose of Endostar (30 mg/kg), low dose of Endostar (8 mg/kg), normal saline, or Bevacizumab (5 mg/kg) was respectively injected into pleural cavity three times with 3-day interval in each group. Transverse computed tomography (CT) was performed to observe pleural fluid formation 14 days after LLC cells injection. Mice were anesthetized and sacrificed 3 days after final administration. The volume of pleural effusion n was measured using 1 ml syringe. Micro blood vessel density (MVD), Lymphatic micro vessel density (LMVD), the expression level of vascular endothelial growth factor A (VEGF-A) and VEGF-C were observed by immunohistochemistry (IHC) staining.</p>
</sec>
<sec>
<title>Results</title>
<p>The volume of pleural effusion as well as the number of pleural tumor foci, MVD and the expression of VEGF-A were significantly reduced in high dose of Endostar treat group. More importantly, LMVD and the expression of VEGF-C were markedly lower in treat group than those in the other three control groups.</p>
</sec>
<sec>
<title>Conclusion</title>
<p>Our work demonstrated that Endostar played an efficient anti-cancer role in MPE through its suppressive effect on angiogenesis and lymphangiogenesis, which provided a certain theoretical basis for the effectiveness of Endostar on the MPE treatment.</p>
</sec>
</abstract>
<funding-group>
<funding-statement>This research was supported by the Natural Science Fund of Jiangsu Province (BK2011658) to Song Yong. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement>
</funding-group>
<counts>
<page-count count="10"></page-count>
</counts>
</article-meta>
</front>
</pmc>
</record>

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