Endostar, a novel recombinant human endostatin, exerts antiangiogenic effect via blocking VEGF-induced tyrosine phosphorylation of KDR/Flk-1 of endothelial cells
Endostar, a novel recombinant human endostatin expressed and purified in Escherichia coli with an additional nine-amino acid sequence and forming another his-tag structure, was approved by the SFDA in 2005 for the treatment of non-small-cell lung cancer. But its mechanism of action has not been illu...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2007-09, Vol.361 (1), p.79-84 |
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| creator | Ling, Yun Yang, Yong Lu, Na You, Qi-dong Wang, Sen Gao, Ying Chen, Yan Guo, Qing-Long |
| description | Endostar, a novel recombinant human endostatin expressed and purified in
Escherichia coli with an additional nine-amino acid sequence and forming another his-tag structure, was approved by the SFDA in 2005 for the treatment of non-small-cell lung cancer. But its mechanism of action has not been illustrated before. In this study, we examined the antiangiogenic activities of endostar
in vitro and
in vivo. The results showed that endostar suppressed the VEGF-stimulated proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs)
in vitro. Endostar blocked microvessel sprouting from rat aortic rings
in vitro. Moreover, it could inhibit the formation of new capillaries from pre-existing vessels in the chicken chorioallantoic membrane (CAM) assay and affect the growth of vessels in tumor. We further found the antiangiogenic effects of endostar were correlated with the VEGF-triggered signaling. Endostar suppressed the VEGF-induced tyrosine phosphorylation of KDR/Flk-1(VEGFR-2) as well as the overall VEGFR-2 expression and the activation of ERK, p38 MAPK, and AKT in HUVECs. Collectively, these data indicated the relationship between endostar and VEGF signal pathways and provided a molecular basis for the antiangiogenic effects of endostar. |
| doi_str_mv | 10.1016/j.bbrc.2007.06.155 |
| format | Article |
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Escherichia coli with an additional nine-amino acid sequence and forming another his-tag structure, was approved by the SFDA in 2005 for the treatment of non-small-cell lung cancer. But its mechanism of action has not been illustrated before. In this study, we examined the antiangiogenic activities of endostar
in vitro and
in vivo. The results showed that endostar suppressed the VEGF-stimulated proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs)
in vitro. Endostar blocked microvessel sprouting from rat aortic rings
in vitro. Moreover, it could inhibit the formation of new capillaries from pre-existing vessels in the chicken chorioallantoic membrane (CAM) assay and affect the growth of vessels in tumor. We further found the antiangiogenic effects of endostar were correlated with the VEGF-triggered signaling. Endostar suppressed the VEGF-induced tyrosine phosphorylation of KDR/Flk-1(VEGFR-2) as well as the overall VEGFR-2 expression and the activation of ERK, p38 MAPK, and AKT in HUVECs. Collectively, these data indicated the relationship between endostar and VEGF signal pathways and provided a molecular basis for the antiangiogenic effects of endostar.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2007.06.155</identifier><identifier>PMID: 17644065</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>60 APPLIED LIFE SCIENCES ; AMINO ACID SEQUENCE ; Angiogenesis ; Angiogenesis Inhibitors - pharmacology ; Animals ; Antineoplastic Agents - pharmacology ; CAPILLARIES ; Carcinoma, Lewis Lung - blood supply ; Carcinoma, Lewis Lung - pathology ; Cell Movement - drug effects ; Chick Embryo ; CHICKENS ; Endostar ; Endostatins - pharmacology ; Endothelial Cells - drug effects ; Endothelial Cells - physiology ; Endothelium, Vascular - cytology ; Endothelium, Vascular - drug effects ; ESCHERICHIA COLI ; FETAL MEMBRANES ; Humans ; HUVEC ; IN VITRO ; In Vitro Techniques ; IN VIVO ; KDR/Flk-1 ; LUNGS ; Mice ; NEOPLASMS ; PHOSPHORYLATION ; Phosphorylation - drug effects ; RATS ; Signal Transduction - drug effects ; TYROSINE ; Tyrosine - metabolism ; Vascular Endothelial Growth Factor A - antagonists & inhibitors ; Vascular Endothelial Growth Factor Receptor-2 - antagonists & inhibitors ; Vascular Endothelial Growth Factor Receptor-2 - chemistry ; Vascular Endothelial Growth Factor Receptor-2 - metabolism ; VEGF ; VEINS</subject><ispartof>Biochemical and biophysical research communications, 2007-09, Vol.361 (1), p.79-84</ispartof><rights>2007 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c479t-75cf48b37c8ff18e3723b46b749419f5b812f79325931294f0a64c226bd37e763</citedby><cites>FETCH-LOGICAL-c479t-75cf48b37c8ff18e3723b46b749419f5b812f79325931294f0a64c226bd37e763</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bbrc.2007.06.155$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17644065$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/20991529$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Ling, Yun</creatorcontrib><creatorcontrib>Yang, Yong</creatorcontrib><creatorcontrib>Lu, Na</creatorcontrib><creatorcontrib>You, Qi-dong</creatorcontrib><creatorcontrib>Wang, Sen</creatorcontrib><creatorcontrib>Gao, Ying</creatorcontrib><creatorcontrib>Chen, Yan</creatorcontrib><creatorcontrib>Guo, Qing-Long</creatorcontrib><title>Endostar, a novel recombinant human endostatin, exerts antiangiogenic effect via blocking VEGF-induced tyrosine phosphorylation of KDR/Flk-1 of endothelial cells</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>Endostar, a novel recombinant human endostatin expressed and purified in
Escherichia coli with an additional nine-amino acid sequence and forming another his-tag structure, was approved by the SFDA in 2005 for the treatment of non-small-cell lung cancer. But its mechanism of action has not been illustrated before. In this study, we examined the antiangiogenic activities of endostar
in vitro and
in vivo. The results showed that endostar suppressed the VEGF-stimulated proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs)
in vitro. Endostar blocked microvessel sprouting from rat aortic rings
in vitro. Moreover, it could inhibit the formation of new capillaries from pre-existing vessels in the chicken chorioallantoic membrane (CAM) assay and affect the growth of vessels in tumor. We further found the antiangiogenic effects of endostar were correlated with the VEGF-triggered signaling. Endostar suppressed the VEGF-induced tyrosine phosphorylation of KDR/Flk-1(VEGFR-2) as well as the overall VEGFR-2 expression and the activation of ERK, p38 MAPK, and AKT in HUVECs. Collectively, these data indicated the relationship between endostar and VEGF signal pathways and provided a molecular basis for the antiangiogenic effects of endostar.</description><subject>60 APPLIED LIFE SCIENCES</subject><subject>AMINO ACID SEQUENCE</subject><subject>Angiogenesis</subject><subject>Angiogenesis Inhibitors - pharmacology</subject><subject>Animals</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>CAPILLARIES</subject><subject>Carcinoma, Lewis Lung - blood supply</subject><subject>Carcinoma, Lewis Lung - pathology</subject><subject>Cell Movement - drug effects</subject><subject>Chick Embryo</subject><subject>CHICKENS</subject><subject>Endostar</subject><subject>Endostatins - pharmacology</subject><subject>Endothelial Cells - drug effects</subject><subject>Endothelial Cells - physiology</subject><subject>Endothelium, Vascular - cytology</subject><subject>Endothelium, Vascular - drug effects</subject><subject>ESCHERICHIA COLI</subject><subject>FETAL MEMBRANES</subject><subject>Humans</subject><subject>HUVEC</subject><subject>IN VITRO</subject><subject>In Vitro Techniques</subject><subject>IN VIVO</subject><subject>KDR/Flk-1</subject><subject>LUNGS</subject><subject>Mice</subject><subject>NEOPLASMS</subject><subject>PHOSPHORYLATION</subject><subject>Phosphorylation - drug effects</subject><subject>RATS</subject><subject>Signal Transduction - drug effects</subject><subject>TYROSINE</subject><subject>Tyrosine - metabolism</subject><subject>Vascular Endothelial Growth Factor A - antagonists & inhibitors</subject><subject>Vascular Endothelial Growth Factor Receptor-2 - antagonists & inhibitors</subject><subject>Vascular Endothelial Growth Factor Receptor-2 - chemistry</subject><subject>Vascular Endothelial Growth Factor Receptor-2 - metabolism</subject><subject>VEGF</subject><subject>VEINS</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkdGKEzEUhgdR3Lr6Al5IQPBqp3uSyWQm4I2s7SouCKLiXchkTtp0p0lNpsU-zr7pZmjBO70IIeQ7_zn_-YviNYU5BSquN_Oui2bOAJo5iDmt6yfFjIKEklHgT4sZAIiSSfrroniR0gaAUi7k8-KCNoJzEPWseFj4PqRRxyuiiQ8HHEhEE7ad89qPZL3fak_wxIzOXxH8g3FMJH867VcurNA7Q9BaNCM5OE26IZh751fk5-J2WTrf7w32ZDzGkJxHsluHlE88DlkveBIs-fLx2_VyuC_p9Jh6jWscnB6IwWFIL4tnVg8JX53vy-LHcvH95lN59_X2882Hu9LwRo5lUxvL265qTGstbbFqWNVx0TVccipt3bWU2UZWrJYVZZJb0IIbxkTXVw02oros3p50s1WnknEjmrUJ3mdjioGUtGYyU-9O1C6G33tMo9q6NM2pPYZ9UiK3gZbBf0EGNM_S0gyyE2jyhlJEq3bRbXU8Kgpqyllt1JSzmnJWIFTOORe9Oavvuy32f0vOwWbg_QnAvLKDwzg5Qp-jcHEy1Af3L_1H_n26OQ</recordid><startdate>20070914</startdate><enddate>20070914</enddate><creator>Ling, Yun</creator><creator>Yang, Yong</creator><creator>Lu, Na</creator><creator>You, Qi-dong</creator><creator>Wang, Sen</creator><creator>Gao, Ying</creator><creator>Chen, Yan</creator><creator>Guo, Qing-Long</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QO</scope><scope>7TM</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope><scope>OTOTI</scope></search><sort><creationdate>20070914</creationdate><title>Endostar, a novel recombinant human endostatin, exerts antiangiogenic effect via blocking VEGF-induced tyrosine phosphorylation of KDR/Flk-1 of endothelial cells</title><author>Ling, Yun ; Yang, Yong ; Lu, Na ; You, Qi-dong ; Wang, Sen ; Gao, Ying ; Chen, Yan ; Guo, Qing-Long</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c479t-75cf48b37c8ff18e3723b46b749419f5b812f79325931294f0a64c226bd37e763</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>60 APPLIED LIFE SCIENCES</topic><topic>AMINO ACID SEQUENCE</topic><topic>Angiogenesis</topic><topic>Angiogenesis Inhibitors - pharmacology</topic><topic>Animals</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>CAPILLARIES</topic><topic>Carcinoma, Lewis Lung - blood supply</topic><topic>Carcinoma, Lewis Lung - pathology</topic><topic>Cell Movement - drug effects</topic><topic>Chick Embryo</topic><topic>CHICKENS</topic><topic>Endostar</topic><topic>Endostatins - pharmacology</topic><topic>Endothelial Cells - drug effects</topic><topic>Endothelial Cells - physiology</topic><topic>Endothelium, Vascular - cytology</topic><topic>Endothelium, Vascular - drug effects</topic><topic>ESCHERICHIA COLI</topic><topic>FETAL MEMBRANES</topic><topic>Humans</topic><topic>HUVEC</topic><topic>IN VITRO</topic><topic>In Vitro Techniques</topic><topic>IN VIVO</topic><topic>KDR/Flk-1</topic><topic>LUNGS</topic><topic>Mice</topic><topic>NEOPLASMS</topic><topic>PHOSPHORYLATION</topic><topic>Phosphorylation - drug effects</topic><topic>RATS</topic><topic>Signal Transduction - drug effects</topic><topic>TYROSINE</topic><topic>Tyrosine - metabolism</topic><topic>Vascular Endothelial Growth Factor A - antagonists & inhibitors</topic><topic>Vascular Endothelial Growth Factor Receptor-2 - antagonists & inhibitors</topic><topic>Vascular Endothelial Growth Factor Receptor-2 - chemistry</topic><topic>Vascular Endothelial Growth Factor Receptor-2 - metabolism</topic><topic>VEGF</topic><topic>VEINS</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ling, Yun</creatorcontrib><creatorcontrib>Yang, Yong</creatorcontrib><creatorcontrib>Lu, Na</creatorcontrib><creatorcontrib>You, Qi-dong</creatorcontrib><creatorcontrib>Wang, Sen</creatorcontrib><creatorcontrib>Gao, Ying</creatorcontrib><creatorcontrib>Chen, Yan</creatorcontrib><creatorcontrib>Guo, Qing-Long</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>OSTI.GOV</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ling, Yun</au><au>Yang, Yong</au><au>Lu, Na</au><au>You, Qi-dong</au><au>Wang, Sen</au><au>Gao, Ying</au><au>Chen, Yan</au><au>Guo, Qing-Long</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Endostar, a novel recombinant human endostatin, exerts antiangiogenic effect via blocking VEGF-induced tyrosine phosphorylation of KDR/Flk-1 of endothelial cells</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2007-09-14</date><risdate>2007</risdate><volume>361</volume><issue>1</issue><spage>79</spage><epage>84</epage><pages>79-84</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>Endostar, a novel recombinant human endostatin expressed and purified in
Escherichia coli with an additional nine-amino acid sequence and forming another his-tag structure, was approved by the SFDA in 2005 for the treatment of non-small-cell lung cancer. But its mechanism of action has not been illustrated before. In this study, we examined the antiangiogenic activities of endostar
in vitro and
in vivo. The results showed that endostar suppressed the VEGF-stimulated proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs)
in vitro. Endostar blocked microvessel sprouting from rat aortic rings
in vitro. Moreover, it could inhibit the formation of new capillaries from pre-existing vessels in the chicken chorioallantoic membrane (CAM) assay and affect the growth of vessels in tumor. We further found the antiangiogenic effects of endostar were correlated with the VEGF-triggered signaling. Endostar suppressed the VEGF-induced tyrosine phosphorylation of KDR/Flk-1(VEGFR-2) as well as the overall VEGFR-2 expression and the activation of ERK, p38 MAPK, and AKT in HUVECs. Collectively, these data indicated the relationship between endostar and VEGF signal pathways and provided a molecular basis for the antiangiogenic effects of endostar.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>17644065</pmid><doi>10.1016/j.bbrc.2007.06.155</doi><tpages>6</tpages></addata></record> |
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| ispartof | Biochemical and biophysical research communications, 2007-09, Vol.361 (1), p.79-84 |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | 60 APPLIED LIFE SCIENCES AMINO ACID SEQUENCE Angiogenesis Angiogenesis Inhibitors - pharmacology Animals Antineoplastic Agents - pharmacology CAPILLARIES Carcinoma, Lewis Lung - blood supply Carcinoma, Lewis Lung - pathology Cell Movement - drug effects Chick Embryo CHICKENS Endostar Endostatins - pharmacology Endothelial Cells - drug effects Endothelial Cells - physiology Endothelium, Vascular - cytology Endothelium, Vascular - drug effects ESCHERICHIA COLI FETAL MEMBRANES Humans HUVEC IN VITRO In Vitro Techniques IN VIVO KDR/Flk-1 LUNGS Mice NEOPLASMS PHOSPHORYLATION Phosphorylation - drug effects RATS Signal Transduction - drug effects TYROSINE Tyrosine - metabolism Vascular Endothelial Growth Factor A - antagonists & inhibitors Vascular Endothelial Growth Factor Receptor-2 - antagonists & inhibitors Vascular Endothelial Growth Factor Receptor-2 - chemistry Vascular Endothelial Growth Factor Receptor-2 - metabolism VEGF VEINS |
| title | Endostar, a novel recombinant human endostatin, exerts antiangiogenic effect via blocking VEGF-induced tyrosine phosphorylation of KDR/Flk-1 of endothelial cells |
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