Gene transfer of endostatin enhances the efficacy of doxorubicin to suppress human hepatocellular carcinomas in mice
Hepatocellular carcinoma (HCC) is one of the most common cancer‐related causes of death, and is chemoresistant to anticancer drugs. Anti‐angiogenic therapy has been shown to enhance the efficacy of chemotherapy to treat solid tumors. The aim of the present study was to determine whether endostatin,...
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| Veröffentlicht in: | Cancer science 2007-09, Vol.98 (9), p.1381-1387 |
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| creator | Liu, Fengjun Tan, Gang Li, Jie Dong, Xuesong Krissansen, Geoffrey W. Sun, Xueying |
| description | Hepatocellular carcinoma (HCC) is one of the most common cancer‐related causes of death, and is chemoresistant to anticancer drugs. Anti‐angiogenic therapy has been shown to enhance the efficacy of chemotherapy to treat solid tumors. The aim of the present study was to determine whether endostatin, a potent antiangiogenic agent, could enhance the efficacy of doxorubicin to combat HCC. An endostatin expression plasmid was constructed and its expression in vitro and in vivo was detected after gene transfer. Recombinant endostatin inhibited angiogenesis in the chorioallantoic membrane assay, and showed synergistic effects with doxorubicin in inhibiting the in vitro proliferation of endothelial cells, but not that of tumor cells. Both endostatin gene therapy and doxorubicin suppressed the growth of subcutaneous human HepG2 tumors established in BALB/c nude mice, and tumor angiogenesis. Combination therapy with endostatin gene therapy and doxorubicin showed a stronger effect in suppressing tumor growth, and tumor angiogenesis, than the respective monotherapies. Gene transfer of endostatin down‐regulated the expression of both hypoxia‐inducible factor‐1α and vascular endothelial growth factor (VEGF), whereas doxorubicin only down‐regulated VEGF expression. Endostatin and doxorubicin synergized to down‐regulate VEGF expression. Endostatin and doxorubicin combination therapy warrants investigation as a therapeutic strategy to combat HCC. (Cancer Sci 2007; 98: 1381–1387) |
| doi_str_mv | 10.1111/j.1349-7006.2007.00542.x |
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Anti‐angiogenic therapy has been shown to enhance the efficacy of chemotherapy to treat solid tumors. The aim of the present study was to determine whether endostatin, a potent antiangiogenic agent, could enhance the efficacy of doxorubicin to combat HCC. An endostatin expression plasmid was constructed and its expression in vitro and in vivo was detected after gene transfer. Recombinant endostatin inhibited angiogenesis in the chorioallantoic membrane assay, and showed synergistic effects with doxorubicin in inhibiting the in vitro proliferation of endothelial cells, but not that of tumor cells. Both endostatin gene therapy and doxorubicin suppressed the growth of subcutaneous human HepG2 tumors established in BALB/c nude mice, and tumor angiogenesis. Combination therapy with endostatin gene therapy and doxorubicin showed a stronger effect in suppressing tumor growth, and tumor angiogenesis, than the respective monotherapies. Gene transfer of endostatin down‐regulated the expression of both hypoxia‐inducible factor‐1α and vascular endothelial growth factor (VEGF), whereas doxorubicin only down‐regulated VEGF expression. Endostatin and doxorubicin synergized to down‐regulate VEGF expression. Endostatin and doxorubicin combination therapy warrants investigation as a therapeutic strategy to combat HCC. (Cancer Sci 2007; 98: 1381–1387)</description><identifier>ISSN: 1347-9032</identifier><identifier>EISSN: 1349-7006</identifier><identifier>DOI: 10.1111/j.1349-7006.2007.00542.x</identifier><identifier>PMID: 17627616</identifier><language>eng</language><publisher>Melbourne, Australia: Blackwell Publishing Asia</publisher><subject>Animals ; Antibiotics, Antineoplastic - administration & dosage ; Biological and medical sciences ; Carcinoma, Hepatocellular - drug therapy ; Cell Line ; Cell Line, Tumor ; Chickens ; Chlorocebus aethiops ; COS Cells ; Doxorubicin - administration & dosage ; Drug Therapy, Combination ; Endostatins - administration & dosage ; Endostatins - genetics ; Gastroenterology. Liver. Pancreas. Abdomen ; Gene Transfer Techniques ; Humans ; Injections, Intralesional ; Liver Neoplasms, Experimental - prevention & control ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Male ; Medical sciences ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Original ; Recombinant Proteins - administration & dosage ; Recombinant Proteins - genetics ; Tumors</subject><ispartof>Cancer science, 2007-09, Vol.98 (9), p.1381-1387</ispartof><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6522-4c74abd3c281384b56f1d5d8f68b44f56ae42baa58beb167bd6dde4bba3d23c63</citedby><cites>FETCH-LOGICAL-c6522-4c74abd3c281384b56f1d5d8f68b44f56ae42baa58beb167bd6dde4bba3d23c63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11160007/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11160007/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,1417,11562,27924,27925,45574,45575,46052,46476,53791,53793</link.rule.ids><linktorsrc>$$Uhttps://onlinelibrary.wiley.com/doi/abs/10.1111%2Fj.1349-7006.2007.00542.x$$EView_record_in_Wiley-Blackwell$$FView_record_in_$$GWiley-Blackwell</linktorsrc><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19020928$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17627616$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Fengjun</creatorcontrib><creatorcontrib>Tan, Gang</creatorcontrib><creatorcontrib>Li, Jie</creatorcontrib><creatorcontrib>Dong, Xuesong</creatorcontrib><creatorcontrib>Krissansen, Geoffrey W.</creatorcontrib><creatorcontrib>Sun, Xueying</creatorcontrib><title>Gene transfer of endostatin enhances the efficacy of doxorubicin to suppress human hepatocellular carcinomas in mice</title><title>Cancer science</title><addtitle>Cancer Sci</addtitle><description>Hepatocellular carcinoma (HCC) is one of the most common cancer‐related causes of death, and is chemoresistant to anticancer drugs. Anti‐angiogenic therapy has been shown to enhance the efficacy of chemotherapy to treat solid tumors. The aim of the present study was to determine whether endostatin, a potent antiangiogenic agent, could enhance the efficacy of doxorubicin to combat HCC. An endostatin expression plasmid was constructed and its expression in vitro and in vivo was detected after gene transfer. Recombinant endostatin inhibited angiogenesis in the chorioallantoic membrane assay, and showed synergistic effects with doxorubicin in inhibiting the in vitro proliferation of endothelial cells, but not that of tumor cells. Both endostatin gene therapy and doxorubicin suppressed the growth of subcutaneous human HepG2 tumors established in BALB/c nude mice, and tumor angiogenesis. Combination therapy with endostatin gene therapy and doxorubicin showed a stronger effect in suppressing tumor growth, and tumor angiogenesis, than the respective monotherapies. Gene transfer of endostatin down‐regulated the expression of both hypoxia‐inducible factor‐1α and vascular endothelial growth factor (VEGF), whereas doxorubicin only down‐regulated VEGF expression. Endostatin and doxorubicin synergized to down‐regulate VEGF expression. Endostatin and doxorubicin combination therapy warrants investigation as a therapeutic strategy to combat HCC. (Cancer Sci 2007; 98: 1381–1387)</description><subject>Animals</subject><subject>Antibiotics, Antineoplastic - administration & dosage</subject><subject>Biological and medical sciences</subject><subject>Carcinoma, Hepatocellular - drug therapy</subject><subject>Cell Line</subject><subject>Cell Line, Tumor</subject><subject>Chickens</subject><subject>Chlorocebus aethiops</subject><subject>COS Cells</subject><subject>Doxorubicin - administration & dosage</subject><subject>Drug Therapy, Combination</subject><subject>Endostatins - administration & dosage</subject><subject>Endostatins - genetics</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Gene Transfer Techniques</subject><subject>Humans</subject><subject>Injections, Intralesional</subject><subject>Liver Neoplasms, Experimental - prevention & control</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Original</subject><subject>Recombinant Proteins - administration & dosage</subject><subject>Recombinant Proteins - genetics</subject><subject>Tumors</subject><issn>1347-9032</issn><issn>1349-7006</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU1v1DAQhiMEoqXwF5AvcEuwHcdxJCRUraAgVeIAnC1_jIlXSRzsBHb_PU531cIJfPFI88w7H29RIIIrkt-bfUVq1pUtxryiGLcVxg2j1eFRcXmfeHwXt2WHa3pRPEtpj3HNWceeFhek5bTlhF8Wyw1MgJaopuQgouAQTDakRS1-ymGvJgMJLT0gcM4bZY4bY8MhxFV7k6EloLTOc4SUUL-OakI9zGoJBoZhHVRERsXMhVEllPHRG3hePHFqSPDi_F8V3z68_7r7WN5-vvm0u74tDW8oLZlpmdK2NlSQWjDdcEdsY4XjQjPmGq6AUa1UIzRowlttubXAtFa1pbXh9VXx7qQ7r3oEa2DKiw5yjn5U8SiD8vLvzOR7-T38lPnGHOe7ZoXXZ4UYfqyQFjn6tG2mJghrklyQhgvB_glSLAjmbFMUJ9DEkFIEdz8OwVtfIvdy81BuHsrNXHlnrjzk0pd_rvNQeHYzA6_OgEpGDS67anx64DpMcUdF5t6euF9-gON_DyB3119yUP8Gn_zDog</recordid><startdate>200709</startdate><enddate>200709</enddate><creator>Liu, Fengjun</creator><creator>Tan, Gang</creator><creator>Li, Jie</creator><creator>Dong, Xuesong</creator><creator>Krissansen, Geoffrey W.</creator><creator>Sun, Xueying</creator><general>Blackwell Publishing Asia</general><general>Blackwell</general><scope>IQODW</scope><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>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>200709</creationdate><title>Gene transfer of endostatin enhances the efficacy of doxorubicin to suppress human hepatocellular carcinomas in mice</title><author>Liu, Fengjun ; Tan, Gang ; Li, Jie ; Dong, Xuesong ; Krissansen, Geoffrey W. ; Sun, Xueying</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6522-4c74abd3c281384b56f1d5d8f68b44f56ae42baa58beb167bd6dde4bba3d23c63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Animals</topic><topic>Antibiotics, Antineoplastic - administration & dosage</topic><topic>Biological and medical sciences</topic><topic>Carcinoma, Hepatocellular - drug therapy</topic><topic>Cell Line</topic><topic>Cell Line, Tumor</topic><topic>Chickens</topic><topic>Chlorocebus aethiops</topic><topic>COS Cells</topic><topic>Doxorubicin - administration & dosage</topic><topic>Drug Therapy, Combination</topic><topic>Endostatins - administration & dosage</topic><topic>Endostatins - genetics</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Gene Transfer Techniques</topic><topic>Humans</topic><topic>Injections, Intralesional</topic><topic>Liver Neoplasms, Experimental - prevention & control</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Original</topic><topic>Recombinant Proteins - administration & dosage</topic><topic>Recombinant Proteins - genetics</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Fengjun</creatorcontrib><creatorcontrib>Tan, Gang</creatorcontrib><creatorcontrib>Li, Jie</creatorcontrib><creatorcontrib>Dong, Xuesong</creatorcontrib><creatorcontrib>Krissansen, Geoffrey W.</creatorcontrib><creatorcontrib>Sun, Xueying</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Liu, Fengjun</au><au>Tan, Gang</au><au>Li, Jie</au><au>Dong, Xuesong</au><au>Krissansen, Geoffrey W.</au><au>Sun, Xueying</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Gene transfer of endostatin enhances the efficacy of doxorubicin to suppress human hepatocellular carcinomas in mice</atitle><jtitle>Cancer science</jtitle><addtitle>Cancer Sci</addtitle><date>2007-09</date><risdate>2007</risdate><volume>98</volume><issue>9</issue><spage>1381</spage><epage>1387</epage><pages>1381-1387</pages><issn>1347-9032</issn><eissn>1349-7006</eissn><abstract>Hepatocellular carcinoma (HCC) is one of the most common cancer‐related causes of death, and is chemoresistant to anticancer drugs. Anti‐angiogenic therapy has been shown to enhance the efficacy of chemotherapy to treat solid tumors. The aim of the present study was to determine whether endostatin, a potent antiangiogenic agent, could enhance the efficacy of doxorubicin to combat HCC. An endostatin expression plasmid was constructed and its expression in vitro and in vivo was detected after gene transfer. Recombinant endostatin inhibited angiogenesis in the chorioallantoic membrane assay, and showed synergistic effects with doxorubicin in inhibiting the in vitro proliferation of endothelial cells, but not that of tumor cells. Both endostatin gene therapy and doxorubicin suppressed the growth of subcutaneous human HepG2 tumors established in BALB/c nude mice, and tumor angiogenesis. Combination therapy with endostatin gene therapy and doxorubicin showed a stronger effect in suppressing tumor growth, and tumor angiogenesis, than the respective monotherapies. Gene transfer of endostatin down‐regulated the expression of both hypoxia‐inducible factor‐1α and vascular endothelial growth factor (VEGF), whereas doxorubicin only down‐regulated VEGF expression. Endostatin and doxorubicin synergized to down‐regulate VEGF expression. Endostatin and doxorubicin combination therapy warrants investigation as a therapeutic strategy to combat HCC. (Cancer Sci 2007; 98: 1381–1387)</abstract><cop>Melbourne, Australia</cop><pub>Blackwell Publishing Asia</pub><pmid>17627616</pmid><doi>10.1111/j.1349-7006.2007.00542.x</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antibiotics, Antineoplastic - administration & dosage Biological and medical sciences Carcinoma, Hepatocellular - drug therapy Cell Line Cell Line, Tumor Chickens Chlorocebus aethiops COS Cells Doxorubicin - administration & dosage Drug Therapy, Combination Endostatins - administration & dosage Endostatins - genetics Gastroenterology. Liver. Pancreas. Abdomen Gene Transfer Techniques Humans Injections, Intralesional Liver Neoplasms, Experimental - prevention & control Liver. Biliary tract. Portal circulation. Exocrine pancreas Male Medical sciences Mice Mice, Inbred BALB C Mice, Nude Original Recombinant Proteins - administration & dosage Recombinant Proteins - genetics Tumors |
| title | Gene transfer of endostatin enhances the efficacy of doxorubicin to suppress human hepatocellular carcinomas in mice |
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