Kallikrein-binding protein suppresses growth of hepatocellular carcinoma by anti-angiogenic activity
Abstract Effect of kallikrein-binding protein (KBP), an endogenous angiogenic inhibitor, on the growth of hepatocellular carcinoma and the possible mechanism were investigated. KBP inhibited proliferation and induced apoptosis of endothelial cells, but had no effect on the proliferation and apoptosi...
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| Veröffentlicht in: | Cancer letters 2007-11, Vol.257 (1), p.97-106 |
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| container_title | Cancer letters |
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| creator | Lu, Lei Yang, Zhonghan Zhu, Baohe Fang, Shuhuan Yang, Xia Cai, Weibin Li, Chaoyang Ma, Jian-xing Gao, Guoquan |
| description | Abstract Effect of kallikrein-binding protein (KBP), an endogenous angiogenic inhibitor, on the growth of hepatocellular carcinoma and the possible mechanism were investigated. KBP inhibited proliferation and induced apoptosis of endothelial cells, but had no effect on the proliferation and apoptosis of hepatocarcinoma cell line HepG2. Intraperitoneal injection of KBP significantly suppressed the tumor growth and inhibited intratumoral neovascularization both in grafted hepatocarcinoma mice and xenografted hepatocarcinoma athymic mice. Moreover, KBP reduced expression of VEGF and HIF-1α nuclear translocation in HepG2 cells and xenografts. Down-regulation of VEGF in tumor cells through inhibiting HIF-1α may represent a novel mechanism for the anti-angiogenic and anti-tumor activity of KBP. |
| doi_str_mv | 10.1016/j.canlet.2007.07.008 |
| format | Article |
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KBP inhibited proliferation and induced apoptosis of endothelial cells, but had no effect on the proliferation and apoptosis of hepatocarcinoma cell line HepG2. Intraperitoneal injection of KBP significantly suppressed the tumor growth and inhibited intratumoral neovascularization both in grafted hepatocarcinoma mice and xenografted hepatocarcinoma athymic mice. Moreover, KBP reduced expression of VEGF and HIF-1α nuclear translocation in HepG2 cells and xenografts. Down-regulation of VEGF in tumor cells through inhibiting HIF-1α may represent a novel mechanism for the anti-angiogenic and anti-tumor activity of KBP.</description><identifier>ISSN: 0304-3835</identifier><identifier>EISSN: 1872-7980</identifier><identifier>DOI: 10.1016/j.canlet.2007.07.008</identifier><identifier>PMID: 17714861</identifier><language>eng</language><publisher>Ireland: Elsevier Ireland Ltd</publisher><subject>Angiogenesis ; Angiogenesis Inhibitors - pharmacology ; Animals ; Apoptosis ; Carcinoma, Hepatocellular - metabolism ; Cell growth ; Cell Line, Tumor ; Flow cytometry ; Gene expression ; Gene Expression Regulation, Neoplastic ; Hematology, Oncology and Palliative Medicine ; Hepatocellular carcinoma ; HIF-1α ; Humans ; Hypoxia ; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism ; KBP ; Laboratory animals ; Liver cancer ; Liver Neoplasms - metabolism ; Male ; Mice ; Neoplasm Transplantation ; Neovascularization, Pathologic ; Proteins ; Rodents ; Science ; Serpins - metabolism ; Studies ; Vascular Endothelial Growth Factor A - metabolism ; VEGF</subject><ispartof>Cancer letters, 2007-11, Vol.257 (1), p.97-106</ispartof><rights>Elsevier Ireland Ltd</rights><rights>2007 Elsevier Ireland Ltd</rights><rights>Copyright Elsevier Limited Nov 8, 2007</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c443t-481a4d9c75bfc122cb1f0e69b5a169f9be6e20c6023195eb5dafb0a00674777c3</citedby><cites>FETCH-LOGICAL-c443t-481a4d9c75bfc122cb1f0e69b5a169f9be6e20c6023195eb5dafb0a00674777c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.canlet.2007.07.008$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3549,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17714861$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lu, Lei</creatorcontrib><creatorcontrib>Yang, Zhonghan</creatorcontrib><creatorcontrib>Zhu, Baohe</creatorcontrib><creatorcontrib>Fang, Shuhuan</creatorcontrib><creatorcontrib>Yang, Xia</creatorcontrib><creatorcontrib>Cai, Weibin</creatorcontrib><creatorcontrib>Li, Chaoyang</creatorcontrib><creatorcontrib>Ma, Jian-xing</creatorcontrib><creatorcontrib>Gao, Guoquan</creatorcontrib><title>Kallikrein-binding protein suppresses growth of hepatocellular carcinoma by anti-angiogenic activity</title><title>Cancer letters</title><addtitle>Cancer Lett</addtitle><description>Abstract Effect of kallikrein-binding protein (KBP), an endogenous angiogenic inhibitor, on the growth of hepatocellular carcinoma and the possible mechanism were investigated. KBP inhibited proliferation and induced apoptosis of endothelial cells, but had no effect on the proliferation and apoptosis of hepatocarcinoma cell line HepG2. Intraperitoneal injection of KBP significantly suppressed the tumor growth and inhibited intratumoral neovascularization both in grafted hepatocarcinoma mice and xenografted hepatocarcinoma athymic mice. Moreover, KBP reduced expression of VEGF and HIF-1α nuclear translocation in HepG2 cells and xenografts. Down-regulation of VEGF in tumor cells through inhibiting HIF-1α may represent a novel mechanism for the anti-angiogenic and anti-tumor activity of KBP.</description><subject>Angiogenesis</subject><subject>Angiogenesis Inhibitors - pharmacology</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Carcinoma, Hepatocellular - metabolism</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Flow cytometry</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Hepatocellular carcinoma</subject><subject>HIF-1α</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>Hypoxia-Inducible Factor 1, alpha Subunit - metabolism</subject><subject>KBP</subject><subject>Laboratory animals</subject><subject>Liver cancer</subject><subject>Liver Neoplasms - metabolism</subject><subject>Male</subject><subject>Mice</subject><subject>Neoplasm Transplantation</subject><subject>Neovascularization, Pathologic</subject><subject>Proteins</subject><subject>Rodents</subject><subject>Science</subject><subject>Serpins - metabolism</subject><subject>Studies</subject><subject>Vascular Endothelial Growth Factor A - metabolism</subject><subject>VEGF</subject><issn>0304-3835</issn><issn>1872-7980</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUk2LFDEQDaK44-g_EGkQvPVY6aST7osgi1-44EE9h3S6ejazPUmbpFfm35swAwt7EQqqAq9eqt4rQl5T2FGg4v1hZ7SbMe0aALkrAd0TsqGdbGrZd_CUbIABr1nH2ivyIsYDALRcts_JFZWS8k7QDRm_63m2dwGtqwfrRuv21RJ8yu8qrssSMEaM1T74v-m28lN1i4tO3uA8r7MOldHBWOePuhpOlXbJ1trtrd-js6bSJtl7m04vybNJzxFfXfKW_P786df11_rmx5dv1x9vasM5SzXvqOZjb2Q7TIY2jRnoBCj6odVU9FM_oMAGjICG0b7FoR31NIAGEJJLKQ3bkndn3rzBnxVjUkcby6jaoV-jEh1jjYA-A98-Ah78GlyeTdG2iMRplm1L-Bllgo8x4KSWYI86nBQFVTxQB3X2QBUPVAkobW8u5OtwxPGh6SJ6Bnw4AzBrcW8xqGgsOoOjDWiSGr393w-PCcxss-B6vsMTxoddVGwUqJ_lDsoZgIRcNoz9AzkBsAQ</recordid><startdate>20071108</startdate><enddate>20071108</enddate><creator>Lu, Lei</creator><creator>Yang, Zhonghan</creator><creator>Zhu, Baohe</creator><creator>Fang, Shuhuan</creator><creator>Yang, Xia</creator><creator>Cai, Weibin</creator><creator>Li, Chaoyang</creator><creator>Ma, Jian-xing</creator><creator>Gao, Guoquan</creator><general>Elsevier Ireland Ltd</general><general>Elsevier Limited</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>7TO</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope></search><sort><creationdate>20071108</creationdate><title>Kallikrein-binding protein suppresses growth of hepatocellular carcinoma by anti-angiogenic activity</title><author>Lu, Lei ; Yang, Zhonghan ; Zhu, Baohe ; Fang, Shuhuan ; Yang, Xia ; Cai, Weibin ; Li, Chaoyang ; Ma, Jian-xing ; Gao, Guoquan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c443t-481a4d9c75bfc122cb1f0e69b5a169f9be6e20c6023195eb5dafb0a00674777c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Angiogenesis</topic><topic>Angiogenesis Inhibitors - pharmacology</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Carcinoma, Hepatocellular - metabolism</topic><topic>Cell growth</topic><topic>Cell Line, Tumor</topic><topic>Flow cytometry</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Hepatocellular carcinoma</topic><topic>HIF-1α</topic><topic>Humans</topic><topic>Hypoxia</topic><topic>Hypoxia-Inducible Factor 1, alpha Subunit - metabolism</topic><topic>KBP</topic><topic>Laboratory animals</topic><topic>Liver cancer</topic><topic>Liver Neoplasms - metabolism</topic><topic>Male</topic><topic>Mice</topic><topic>Neoplasm Transplantation</topic><topic>Neovascularization, Pathologic</topic><topic>Proteins</topic><topic>Rodents</topic><topic>Science</topic><topic>Serpins - metabolism</topic><topic>Studies</topic><topic>Vascular Endothelial Growth Factor A - metabolism</topic><topic>VEGF</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lu, Lei</creatorcontrib><creatorcontrib>Yang, Zhonghan</creatorcontrib><creatorcontrib>Zhu, Baohe</creatorcontrib><creatorcontrib>Fang, Shuhuan</creatorcontrib><creatorcontrib>Yang, Xia</creatorcontrib><creatorcontrib>Cai, Weibin</creatorcontrib><creatorcontrib>Li, Chaoyang</creatorcontrib><creatorcontrib>Ma, Jian-xing</creatorcontrib><creatorcontrib>Gao, Guoquan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lu, Lei</au><au>Yang, Zhonghan</au><au>Zhu, Baohe</au><au>Fang, Shuhuan</au><au>Yang, Xia</au><au>Cai, Weibin</au><au>Li, Chaoyang</au><au>Ma, Jian-xing</au><au>Gao, Guoquan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Kallikrein-binding protein suppresses growth of hepatocellular carcinoma by anti-angiogenic activity</atitle><jtitle>Cancer letters</jtitle><addtitle>Cancer Lett</addtitle><date>2007-11-08</date><risdate>2007</risdate><volume>257</volume><issue>1</issue><spage>97</spage><epage>106</epage><pages>97-106</pages><issn>0304-3835</issn><eissn>1872-7980</eissn><abstract>Abstract Effect of kallikrein-binding protein (KBP), an endogenous angiogenic inhibitor, on the growth of hepatocellular carcinoma and the possible mechanism were investigated. KBP inhibited proliferation and induced apoptosis of endothelial cells, but had no effect on the proliferation and apoptosis of hepatocarcinoma cell line HepG2. Intraperitoneal injection of KBP significantly suppressed the tumor growth and inhibited intratumoral neovascularization both in grafted hepatocarcinoma mice and xenografted hepatocarcinoma athymic mice. Moreover, KBP reduced expression of VEGF and HIF-1α nuclear translocation in HepG2 cells and xenografts. Down-regulation of VEGF in tumor cells through inhibiting HIF-1α may represent a novel mechanism for the anti-angiogenic and anti-tumor activity of KBP.</abstract><cop>Ireland</cop><pub>Elsevier Ireland Ltd</pub><pmid>17714861</pmid><doi>10.1016/j.canlet.2007.07.008</doi><tpages>10</tpages></addata></record> |
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| ispartof | Cancer letters, 2007-11, Vol.257 (1), p.97-106 |
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| subjects | Angiogenesis Angiogenesis Inhibitors - pharmacology Animals Apoptosis Carcinoma, Hepatocellular - metabolism Cell growth Cell Line, Tumor Flow cytometry Gene expression Gene Expression Regulation, Neoplastic Hematology, Oncology and Palliative Medicine Hepatocellular carcinoma HIF-1α Humans Hypoxia Hypoxia-Inducible Factor 1, alpha Subunit - metabolism KBP Laboratory animals Liver cancer Liver Neoplasms - metabolism Male Mice Neoplasm Transplantation Neovascularization, Pathologic Proteins Rodents Science Serpins - metabolism Studies Vascular Endothelial Growth Factor A - metabolism VEGF |
| title | Kallikrein-binding protein suppresses growth of hepatocellular carcinoma by anti-angiogenic activity |
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