Tumors derived from lung cancer cells respond differently to treatment with sodium valproate (a HDAC inhibitor) in a chicken embryo chorioallantoic membrane model
Lung cancer is the most frequent cause of cancer death. Some human lung malignant tumors have a combined small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) histology, with tumor cell phenotype changing during tumor progression. Valproic acid is used as an anti-seizure medication to...
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Veröffentlicht in: | Histology and histopathology 2022-12, Vol.37 (12), p.1201-1212 |
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container_title | Histology and histopathology |
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creator | Diržiuvienė, Raminta Šlekienė, Lina Palubinskienė, Jolita Balnytė, Ingrida Lasienė, Kristina Stakišaitis, Donatas Valančiūtė, Angelija |
description | Lung cancer is the most frequent cause of cancer death. Some human lung malignant tumors have a combined small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) histology, with tumor cell phenotype changing during tumor progression. Valproic acid is used as an anti-seizure medication to treat migraine, and bipolar mood disorders. Recently, its efficacy as an adjuvant therapy was shown in cancer due to its histone deacetylase (HDAC) inhibitory property. HDACs are upregulated in lung tumors, and HDAC inhibitors, including valproic acid, inhibit endothelial cell proliferation in vitro and in vivo and have antiproliferative and antimigratory properties. We tested valproic acid for possible antiangiogenic and antimigratory effects on experimental lung tumors grafted onto the chicken embryo chorioallantoic membrane (CAM). Tumors were formed from two NSCLC cell lines and a single SCLC cell line. To investigate tumor and CAM interactions, in vivo biomicroscopy, visualization of blood vessels with injected fluorescent dextran, histological, immunohistochemical and histomorphometric methods were applied. Our results showed that a sodium valproate (NaVP) treatment-induced a dose-dependent decrease of experimental tumor invasion into the CAM mesenchyme and a reduction in angiogenesis. Both the invasion and the angiogenic response were dependent on the type of cell line used: invasion and angiogenesis of tumors derived from A549 and NCI-H146 cell lines responded to increasing doses of NaVP from 4 to 8 mM, whereas Sk_Lu_1 cells response were antimigratory and antiangiogenic when NaVP was used up to 6 mM. When 8mM NaVP was used, stimulated invasion and angiogenesis in tumors from Sk_Lu_1 cells were observed. |
doi_str_mv | 10.14670/HH-18-482 |
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Some human lung malignant tumors have a combined small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) histology, with tumor cell phenotype changing during tumor progression. Valproic acid is used as an anti-seizure medication to treat migraine, and bipolar mood disorders. Recently, its efficacy as an adjuvant therapy was shown in cancer due to its histone deacetylase (HDAC) inhibitory property. HDACs are upregulated in lung tumors, and HDAC inhibitors, including valproic acid, inhibit endothelial cell proliferation in vitro and in vivo and have antiproliferative and antimigratory properties. We tested valproic acid for possible antiangiogenic and antimigratory effects on experimental lung tumors grafted onto the chicken embryo chorioallantoic membrane (CAM). Tumors were formed from two NSCLC cell lines and a single SCLC cell line. To investigate tumor and CAM interactions, in vivo biomicroscopy, visualization of blood vessels with injected fluorescent dextran, histological, immunohistochemical and histomorphometric methods were applied. Our results showed that a sodium valproate (NaVP) treatment-induced a dose-dependent decrease of experimental tumor invasion into the CAM mesenchyme and a reduction in angiogenesis. Both the invasion and the angiogenic response were dependent on the type of cell line used: invasion and angiogenesis of tumors derived from A549 and NCI-H146 cell lines responded to increasing doses of NaVP from 4 to 8 mM, whereas Sk_Lu_1 cells response were antimigratory and antiangiogenic when NaVP was used up to 6 mM. When 8mM NaVP was used, stimulated invasion and angiogenesis in tumors from Sk_Lu_1 cells were observed.</description><identifier>EISSN: 1699-5848</identifier><identifier>DOI: 10.14670/HH-18-482</identifier><identifier>PMID: 35703146</identifier><language>eng</language><publisher>Spain</publisher><subject>Animals ; Carcinoma, Non-Small-Cell Lung - pathology ; Cell Line, Tumor ; Chick Embryo ; Chickens ; Chorioallantoic Membrane - pathology ; Histone Deacetylase Inhibitors - pharmacology ; Humans ; Lung - metabolism ; Lung Neoplasms - metabolism ; Small Cell Lung Carcinoma - metabolism ; Valproic Acid - pharmacology</subject><ispartof>Histology and histopathology, 2022-12, Vol.37 (12), p.1201-1212</ispartof><rights>The Author(s) 2022. Open Access. 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Some human lung malignant tumors have a combined small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) histology, with tumor cell phenotype changing during tumor progression. Valproic acid is used as an anti-seizure medication to treat migraine, and bipolar mood disorders. Recently, its efficacy as an adjuvant therapy was shown in cancer due to its histone deacetylase (HDAC) inhibitory property. HDACs are upregulated in lung tumors, and HDAC inhibitors, including valproic acid, inhibit endothelial cell proliferation in vitro and in vivo and have antiproliferative and antimigratory properties. We tested valproic acid for possible antiangiogenic and antimigratory effects on experimental lung tumors grafted onto the chicken embryo chorioallantoic membrane (CAM). Tumors were formed from two NSCLC cell lines and a single SCLC cell line. To investigate tumor and CAM interactions, in vivo biomicroscopy, visualization of blood vessels with injected fluorescent dextran, histological, immunohistochemical and histomorphometric methods were applied. Our results showed that a sodium valproate (NaVP) treatment-induced a dose-dependent decrease of experimental tumor invasion into the CAM mesenchyme and a reduction in angiogenesis. Both the invasion and the angiogenic response were dependent on the type of cell line used: invasion and angiogenesis of tumors derived from A549 and NCI-H146 cell lines responded to increasing doses of NaVP from 4 to 8 mM, whereas Sk_Lu_1 cells response were antimigratory and antiangiogenic when NaVP was used up to 6 mM. When 8mM NaVP was used, stimulated invasion and angiogenesis in tumors from Sk_Lu_1 cells were observed.</description><subject>Animals</subject><subject>Carcinoma, Non-Small-Cell Lung - pathology</subject><subject>Cell Line, Tumor</subject><subject>Chick Embryo</subject><subject>Chickens</subject><subject>Chorioallantoic Membrane - pathology</subject><subject>Histone Deacetylase Inhibitors - pharmacology</subject><subject>Humans</subject><subject>Lung - metabolism</subject><subject>Lung Neoplasms - metabolism</subject><subject>Small Cell Lung Carcinoma - metabolism</subject><subject>Valproic Acid - pharmacology</subject><issn>1699-5848</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1kM1u2zAQhIkCQZ2mvfQBgj26ByWifijqGDhJHcBALu7ZWJHLmg0pOiSVwq_TJ42MOqfdWXwYzCxj33l5wxvRlbfrdcFl0cjqE7vkou-LVjZywb6k9Kcsq6pv289sUbddWc_8Jfu3nXyICTRF-0YaTAwe3DT-BoWjogiKnEsQKR3CqEFbYyjSmN0RcoAcCbOfJfy1eQ8paDt5eEN3iAEzwRJhfX-3Ajvu7WBziD_mFRDU3qoXGoH8EI9hliHagM7hmINV4E93HAl80OS-sguDLtG387xivx4ftqt1sXn--bS62xQH3vBcCC06o3SrCCvRYYVcS4FciG5QnErZG9FIMm2DdYsGha4kr0spu4H6hpSpr9jyv-8c_nWilHfeplP9OUmY0m52FX1VN1U7o9dndBo86d0hWo_xuPv4a_0O9s167Q</recordid><startdate>202212</startdate><enddate>202212</enddate><creator>Diržiuvienė, Raminta</creator><creator>Šlekienė, Lina</creator><creator>Palubinskienė, Jolita</creator><creator>Balnytė, Ingrida</creator><creator>Lasienė, Kristina</creator><creator>Stakišaitis, Donatas</creator><creator>Valančiūtė, Angelija</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>202212</creationdate><title>Tumors derived from lung cancer cells respond differently to treatment with sodium valproate (a HDAC inhibitor) in a chicken embryo chorioallantoic membrane model</title><author>Diržiuvienė, Raminta ; Šlekienė, Lina ; Palubinskienė, Jolita ; Balnytė, Ingrida ; Lasienė, Kristina ; Stakišaitis, Donatas ; Valančiūtė, Angelija</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p141t-6d67fcd5cea267a2a1d86a1667bc1e089f648ef54a35afa6d28130887be94ecf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Animals</topic><topic>Carcinoma, Non-Small-Cell Lung - pathology</topic><topic>Cell Line, Tumor</topic><topic>Chick Embryo</topic><topic>Chickens</topic><topic>Chorioallantoic Membrane - pathology</topic><topic>Histone Deacetylase Inhibitors - pharmacology</topic><topic>Humans</topic><topic>Lung - metabolism</topic><topic>Lung Neoplasms - metabolism</topic><topic>Small Cell Lung Carcinoma - metabolism</topic><topic>Valproic Acid - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Diržiuvienė, Raminta</creatorcontrib><creatorcontrib>Šlekienė, Lina</creatorcontrib><creatorcontrib>Palubinskienė, Jolita</creatorcontrib><creatorcontrib>Balnytė, Ingrida</creatorcontrib><creatorcontrib>Lasienė, Kristina</creatorcontrib><creatorcontrib>Stakišaitis, Donatas</creatorcontrib><creatorcontrib>Valančiūtė, Angelija</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Histology and histopathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Diržiuvienė, Raminta</au><au>Šlekienė, Lina</au><au>Palubinskienė, Jolita</au><au>Balnytė, Ingrida</au><au>Lasienė, Kristina</au><au>Stakišaitis, Donatas</au><au>Valančiūtė, Angelija</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tumors derived from lung cancer cells respond differently to treatment with sodium valproate (a HDAC inhibitor) in a chicken embryo chorioallantoic membrane model</atitle><jtitle>Histology and histopathology</jtitle><addtitle>Histol Histopathol</addtitle><date>2022-12</date><risdate>2022</risdate><volume>37</volume><issue>12</issue><spage>1201</spage><epage>1212</epage><pages>1201-1212</pages><eissn>1699-5848</eissn><abstract>Lung cancer is the most frequent cause of cancer death. Some human lung malignant tumors have a combined small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) histology, with tumor cell phenotype changing during tumor progression. Valproic acid is used as an anti-seizure medication to treat migraine, and bipolar mood disorders. Recently, its efficacy as an adjuvant therapy was shown in cancer due to its histone deacetylase (HDAC) inhibitory property. HDACs are upregulated in lung tumors, and HDAC inhibitors, including valproic acid, inhibit endothelial cell proliferation in vitro and in vivo and have antiproliferative and antimigratory properties. We tested valproic acid for possible antiangiogenic and antimigratory effects on experimental lung tumors grafted onto the chicken embryo chorioallantoic membrane (CAM). Tumors were formed from two NSCLC cell lines and a single SCLC cell line. To investigate tumor and CAM interactions, in vivo biomicroscopy, visualization of blood vessels with injected fluorescent dextran, histological, immunohistochemical and histomorphometric methods were applied. Our results showed that a sodium valproate (NaVP) treatment-induced a dose-dependent decrease of experimental tumor invasion into the CAM mesenchyme and a reduction in angiogenesis. Both the invasion and the angiogenic response were dependent on the type of cell line used: invasion and angiogenesis of tumors derived from A549 and NCI-H146 cell lines responded to increasing doses of NaVP from 4 to 8 mM, whereas Sk_Lu_1 cells response were antimigratory and antiangiogenic when NaVP was used up to 6 mM. When 8mM NaVP was used, stimulated invasion and angiogenesis in tumors from Sk_Lu_1 cells were observed.</abstract><cop>Spain</cop><pmid>35703146</pmid><doi>10.14670/HH-18-482</doi><tpages>12</tpages></addata></record> |
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subjects | Animals Carcinoma, Non-Small-Cell Lung - pathology Cell Line, Tumor Chick Embryo Chickens Chorioallantoic Membrane - pathology Histone Deacetylase Inhibitors - pharmacology Humans Lung - metabolism Lung Neoplasms - metabolism Small Cell Lung Carcinoma - metabolism Valproic Acid - pharmacology |
title | Tumors derived from lung cancer cells respond differently to treatment with sodium valproate (a HDAC inhibitor) in a chicken embryo chorioallantoic membrane model |
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