Inhibition of Na+ /H+ exchanger 1 by 5-(N-ethyl-N-isopropyl) amiloride reduces hypoxia-induced hepatocellular carcinoma invasion and motility
Abstract Na+ /H+ exchanger 1 (NHE1) plays a significant role in tumor metastasis. However, the exact mechanisms by which NHE1 mediates cell invasion and migration, especially in hepatocellular carcinoma (HCC), are not yet known. In the current study, we show for the first time that the inhibition of...
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| Veröffentlicht in: | Cancer letters 2010-09, Vol.295 (2), p.198-204 |
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| creator | Yang, Xuekang Wang, Desheng Dong, Wei Song, Zhenshun Dou, Kefeng |
| description | Abstract Na+ /H+ exchanger 1 (NHE1) plays a significant role in tumor metastasis. However, the exact mechanisms by which NHE1 mediates cell invasion and migration, especially in hepatocellular carcinoma (HCC), are not yet known. In the current study, we show for the first time that the inhibition of NHE1 by 5-(N-ethyl-N-isopropyl) amiloride (EIPA) is able to suppress migration and invasion of HepG2 cells under hypoxic conditions. In addition, hypoxia activated ERK1/2, which in turn promoted the production of MMP-2, MMP-9 and VEGF. EIPA’s suppressive role was determined to act through down-regulation of MMP-2, MMP-9 and VEGF in an ERK1/2 dependent manner. The data demonstrate that NHE1 plays a role in HCC invasion and that NHE1 may be a potential therapeutic target for HCC treatment. |
| doi_str_mv | 10.1016/j.canlet.2010.03.001 |
| format | Article |
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However, the exact mechanisms by which NHE1 mediates cell invasion and migration, especially in hepatocellular carcinoma (HCC), are not yet known. In the current study, we show for the first time that the inhibition of NHE1 by 5-(N-ethyl-N-isopropyl) amiloride (EIPA) is able to suppress migration and invasion of HepG2 cells under hypoxic conditions. In addition, hypoxia activated ERK1/2, which in turn promoted the production of MMP-2, MMP-9 and VEGF. EIPA’s suppressive role was determined to act through down-regulation of MMP-2, MMP-9 and VEGF in an ERK1/2 dependent manner. The data demonstrate that NHE1 plays a role in HCC invasion and that NHE1 may be a potential therapeutic target for HCC treatment.</description><identifier>ISSN: 0304-3835</identifier><identifier>EISSN: 1872-7980</identifier><identifier>DOI: 10.1016/j.canlet.2010.03.001</identifier><identifier>PMID: 20338684</identifier><language>eng</language><publisher>Ireland: Elsevier Ireland Ltd</publisher><subject>Acidification ; Amiloride - analogs & derivatives ; Amiloride - pharmacology ; Carcinoma, Hepatocellular - pathology ; Cation Transport Proteins - antagonists & inhibitors ; Cation Transport Proteins - physiology ; Cell culture ; Cell Hypoxia ; Cell Movement ; Extracellular Signal-Regulated MAP Kinases - antagonists & inhibitors ; Hematology, Oncology and Palliative Medicine ; Hep G2 Cells ; Hepatocellular carcinoma ; Humans ; Hydrogen-Ion Concentration ; Hypoxia ; Invasion ; Kinases ; Liver cancer ; Liver Neoplasms - pathology ; Matrix Metalloproteinase 2 - analysis ; Matrix Metalloproteinase 9 - analysis ; Medical prognosis ; Migration ; Mortality ; Motility ; Na +/H + exchanger 1 ; Neoplasm Invasiveness ; Phenols ; Phosphorylation ; Sodium-Hydrogen Exchanger 1 ; Sodium-Hydrogen Exchangers - antagonists & inhibitors ; Sodium-Hydrogen Exchangers - physiology ; Spectrum analysis ; Tumor microenvironment ; Vascular endothelial growth factor ; Vascular Endothelial Growth Factor A - analysis</subject><ispartof>Cancer letters, 2010-09, Vol.295 (2), p.198-204</ispartof><rights>Elsevier Ireland Ltd</rights><rights>2010 Elsevier Ireland Ltd</rights><rights>2010 Elsevier Ireland Ltd. All rights reserved.</rights><rights>Copyright Elsevier Limited Sep 28, 2010</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c510t-b1c1e82cd96d746af4998cbc7a737ff897e7131bc55a39df07811b18836c2c223</citedby><cites>FETCH-LOGICAL-c510t-b1c1e82cd96d746af4998cbc7a737ff897e7131bc55a39df07811b18836c2c223</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.2010.03.001$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20338684$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yang, Xuekang</creatorcontrib><creatorcontrib>Wang, Desheng</creatorcontrib><creatorcontrib>Dong, Wei</creatorcontrib><creatorcontrib>Song, Zhenshun</creatorcontrib><creatorcontrib>Dou, Kefeng</creatorcontrib><title>Inhibition of Na+ /H+ exchanger 1 by 5-(N-ethyl-N-isopropyl) amiloride reduces hypoxia-induced hepatocellular carcinoma invasion and motility</title><title>Cancer letters</title><addtitle>Cancer Lett</addtitle><description>Abstract Na+ /H+ exchanger 1 (NHE1) plays a significant role in tumor metastasis. However, the exact mechanisms by which NHE1 mediates cell invasion and migration, especially in hepatocellular carcinoma (HCC), are not yet known. In the current study, we show for the first time that the inhibition of NHE1 by 5-(N-ethyl-N-isopropyl) amiloride (EIPA) is able to suppress migration and invasion of HepG2 cells under hypoxic conditions. In addition, hypoxia activated ERK1/2, which in turn promoted the production of MMP-2, MMP-9 and VEGF. EIPA’s suppressive role was determined to act through down-regulation of MMP-2, MMP-9 and VEGF in an ERK1/2 dependent manner. The data demonstrate that NHE1 plays a role in HCC invasion and that NHE1 may be a potential therapeutic target for HCC treatment.</description><subject>Acidification</subject><subject>Amiloride - analogs & derivatives</subject><subject>Amiloride - pharmacology</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Cation Transport Proteins - antagonists & inhibitors</subject><subject>Cation Transport Proteins - physiology</subject><subject>Cell culture</subject><subject>Cell Hypoxia</subject><subject>Cell Movement</subject><subject>Extracellular Signal-Regulated MAP Kinases - antagonists & inhibitors</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Hep G2 Cells</subject><subject>Hepatocellular carcinoma</subject><subject>Humans</subject><subject>Hydrogen-Ion Concentration</subject><subject>Hypoxia</subject><subject>Invasion</subject><subject>Kinases</subject><subject>Liver cancer</subject><subject>Liver Neoplasms - pathology</subject><subject>Matrix Metalloproteinase 2 - analysis</subject><subject>Matrix Metalloproteinase 9 - analysis</subject><subject>Medical prognosis</subject><subject>Migration</subject><subject>Mortality</subject><subject>Motility</subject><subject>Na +/H + exchanger 1</subject><subject>Neoplasm Invasiveness</subject><subject>Phenols</subject><subject>Phosphorylation</subject><subject>Sodium-Hydrogen Exchanger 1</subject><subject>Sodium-Hydrogen Exchangers - antagonists & inhibitors</subject><subject>Sodium-Hydrogen Exchangers - physiology</subject><subject>Spectrum analysis</subject><subject>Tumor microenvironment</subject><subject>Vascular endothelial growth factor</subject><subject>Vascular Endothelial Growth Factor A - analysis</subject><issn>0304-3835</issn><issn>1872-7980</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUsFu1TAQjBCIPgp_gJAlDoCqvK7jJHYuSKgCWql6HICz5Tgb4odjp3ZSNR_BP5MoBaReOFlrzczuzmySvKSwp0DL8-NeK2dx3GewfAHbA9BHyY4KnqW8EvA42QGDPGWCFSfJsxiPAFDkvHianGTAmChFvkt-XbnO1GY03hHfkoM6I-eXZwTvdKfcDwyEknomRfr2kOLYzTY9pCb6Ifhhtu-I6o31wTRIAjaTxki6efB3RqXGrXVDOhzU6DVaO1kViFZBG-d7RYy7VXHtqlxDej8aa8b5efKkVTbii_v3NPn-6eO3i8v0-svnq4sP16kuKIxpTTVFkemmKhuel6rNq0roWnPFGW9bUXHklNFaF4ViVdMCF5TWVAhW6kxnGTtN3my6yyI3E8ZR9iauQyqHfoqSM7Y4mHFYkK8fII9-Cm4ZTtICSijLxfYFlW8oHXyMAVs5BNOrMEsKck1LHuWWllzTksDkRnt1Lz7VPTZ_SX_iWQDvNwAuZtwaDDJqg24x1gTUo2y8-V-HhwLaGme0sj9xxvhvFxkzCfLrejHrwVBY2SJjvwGnTrxX</recordid><startdate>20100928</startdate><enddate>20100928</enddate><creator>Yang, Xuekang</creator><creator>Wang, Desheng</creator><creator>Dong, Wei</creator><creator>Song, Zhenshun</creator><creator>Dou, Kefeng</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>20100928</creationdate><title>Inhibition of Na+ /H+ exchanger 1 by 5-(N-ethyl-N-isopropyl) amiloride reduces hypoxia-induced hepatocellular carcinoma invasion and motility</title><author>Yang, Xuekang ; Wang, Desheng ; Dong, Wei ; Song, Zhenshun ; Dou, Kefeng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c510t-b1c1e82cd96d746af4998cbc7a737ff897e7131bc55a39df07811b18836c2c223</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Acidification</topic><topic>Amiloride - analogs & derivatives</topic><topic>Amiloride - pharmacology</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Cation Transport Proteins - antagonists & inhibitors</topic><topic>Cation Transport Proteins - physiology</topic><topic>Cell culture</topic><topic>Cell Hypoxia</topic><topic>Cell Movement</topic><topic>Extracellular Signal-Regulated MAP Kinases - antagonists & inhibitors</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Hep G2 Cells</topic><topic>Hepatocellular carcinoma</topic><topic>Humans</topic><topic>Hydrogen-Ion Concentration</topic><topic>Hypoxia</topic><topic>Invasion</topic><topic>Kinases</topic><topic>Liver cancer</topic><topic>Liver Neoplasms - pathology</topic><topic>Matrix Metalloproteinase 2 - analysis</topic><topic>Matrix Metalloproteinase 9 - analysis</topic><topic>Medical prognosis</topic><topic>Migration</topic><topic>Mortality</topic><topic>Motility</topic><topic>Na +/H + exchanger 1</topic><topic>Neoplasm Invasiveness</topic><topic>Phenols</topic><topic>Phosphorylation</topic><topic>Sodium-Hydrogen Exchanger 1</topic><topic>Sodium-Hydrogen Exchangers - antagonists & inhibitors</topic><topic>Sodium-Hydrogen Exchangers - physiology</topic><topic>Spectrum analysis</topic><topic>Tumor microenvironment</topic><topic>Vascular endothelial growth factor</topic><topic>Vascular Endothelial Growth Factor A - analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yang, Xuekang</creatorcontrib><creatorcontrib>Wang, Desheng</creatorcontrib><creatorcontrib>Dong, Wei</creatorcontrib><creatorcontrib>Song, Zhenshun</creatorcontrib><creatorcontrib>Dou, Kefeng</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>Yang, Xuekang</au><au>Wang, Desheng</au><au>Dong, Wei</au><au>Song, Zhenshun</au><au>Dou, Kefeng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of Na+ /H+ exchanger 1 by 5-(N-ethyl-N-isopropyl) amiloride reduces hypoxia-induced hepatocellular carcinoma invasion and motility</atitle><jtitle>Cancer letters</jtitle><addtitle>Cancer Lett</addtitle><date>2010-09-28</date><risdate>2010</risdate><volume>295</volume><issue>2</issue><spage>198</spage><epage>204</epage><pages>198-204</pages><issn>0304-3835</issn><eissn>1872-7980</eissn><abstract>Abstract Na+ /H+ exchanger 1 (NHE1) plays a significant role in tumor metastasis. However, the exact mechanisms by which NHE1 mediates cell invasion and migration, especially in hepatocellular carcinoma (HCC), are not yet known. In the current study, we show for the first time that the inhibition of NHE1 by 5-(N-ethyl-N-isopropyl) amiloride (EIPA) is able to suppress migration and invasion of HepG2 cells under hypoxic conditions. In addition, hypoxia activated ERK1/2, which in turn promoted the production of MMP-2, MMP-9 and VEGF. EIPA’s suppressive role was determined to act through down-regulation of MMP-2, MMP-9 and VEGF in an ERK1/2 dependent manner. The data demonstrate that NHE1 plays a role in HCC invasion and that NHE1 may be a potential therapeutic target for HCC treatment.</abstract><cop>Ireland</cop><pub>Elsevier Ireland Ltd</pub><pmid>20338684</pmid><doi>10.1016/j.canlet.2010.03.001</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | Cancer letters, 2010-09, Vol.295 (2), p.198-204 |
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| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | Acidification Amiloride - analogs & derivatives Amiloride - pharmacology Carcinoma, Hepatocellular - pathology Cation Transport Proteins - antagonists & inhibitors Cation Transport Proteins - physiology Cell culture Cell Hypoxia Cell Movement Extracellular Signal-Regulated MAP Kinases - antagonists & inhibitors Hematology, Oncology and Palliative Medicine Hep G2 Cells Hepatocellular carcinoma Humans Hydrogen-Ion Concentration Hypoxia Invasion Kinases Liver cancer Liver Neoplasms - pathology Matrix Metalloproteinase 2 - analysis Matrix Metalloproteinase 9 - analysis Medical prognosis Migration Mortality Motility Na +/H + exchanger 1 Neoplasm Invasiveness Phenols Phosphorylation Sodium-Hydrogen Exchanger 1 Sodium-Hydrogen Exchangers - antagonists & inhibitors Sodium-Hydrogen Exchangers - physiology Spectrum analysis Tumor microenvironment Vascular endothelial growth factor Vascular Endothelial Growth Factor A - analysis |
| title | Inhibition of Na+ /H+ exchanger 1 by 5-(N-ethyl-N-isopropyl) amiloride reduces hypoxia-induced hepatocellular carcinoma invasion and motility |
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