Potent growth-inhibitory effect of TRAIL therapy mediated by double-regulated oncolytic adenovirus on osteosarcoma
Osteosarcoma (OS) severely threatens the health of young people and understanding on the molecular mechanisms of OS etiology enables gene therapy to become an effective therapeutic modality. However, insufficient expression level of genes using existing vectors limits the clinical application of gen...
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| Veröffentlicht in: | Molecular and cellular biochemistry 2012-05, Vol.364 (1-2), p.337-344 |
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| creator | Chunbao, Li Qianpeng, Cheng Jia, Liu Bin, Wang Dongfeng, Chen Yujie, Liu |
| description | Osteosarcoma (OS) severely threatens the health of young people and understanding on the molecular mechanisms of OS etiology enables gene therapy to become an effective therapeutic modality. However, insufficient expression level of genes using existing vectors limits the clinical application of gene therapy for OS. To solve the problem, we developed an oncolytic adenoviral vector, OAT, which can selectively and efficiently replicate in OS cells to enhance the expression of transferred genes. We demonstrated that OAT-mediated TRAIL expression is significantly elevated after infection of OS cells than replication-incompetent Ad5 vector. Increased antitumor capacity was observed in OS cells after OAT-TRAIL treatment both in vitro and in vivo. In normal cells, adenoviral replication, TRAIL expression and growth-inhibiting effect were quite limited when OAT-TRAIL was administrated, showing a high biosafety of this oncolytic adenoviral vector. Collectively, we generated an efficient and promising expression vector for OS gene therapy. |
| doi_str_mv | 10.1007/s11010-012-1235-9 |
| format | Article |
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However, insufficient expression level of genes using existing vectors limits the clinical application of gene therapy for OS. To solve the problem, we developed an oncolytic adenoviral vector, OAT, which can selectively and efficiently replicate in OS cells to enhance the expression of transferred genes. We demonstrated that OAT-mediated TRAIL expression is significantly elevated after infection of OS cells than replication-incompetent Ad5 vector. Increased antitumor capacity was observed in OS cells after OAT-TRAIL treatment both in vitro and in vivo. In normal cells, adenoviral replication, TRAIL expression and growth-inhibiting effect were quite limited when OAT-TRAIL was administrated, showing a high biosafety of this oncolytic adenoviral vector. Collectively, we generated an efficient and promising expression vector for OS gene therapy.</description><identifier>ISSN: 0300-8177</identifier><identifier>EISSN: 1573-4919</identifier><identifier>DOI: 10.1007/s11010-012-1235-9</identifier><identifier>PMID: 22354724</identifier><language>eng</language><publisher>Boston: Springer US</publisher><subject>Adenoviridae - genetics ; Adenovirus ; Adenoviruses ; Animals ; Biochemistry ; Biomedical and Life Sciences ; Biosafety ; Bone cancer ; Bone Neoplasms - genetics ; Bone Neoplasms - therapy ; Cardiology ; Cell Line, Tumor ; Development and progression ; Etiology ; Expression vectors ; Fibroblasts - cytology ; Gene expression ; Gene therapy ; Genetic engineering ; Genetic Therapy - methods ; Genetic Vectors ; Green Fluorescent Proteins - genetics ; Growth ; Health aspects ; Humans ; Infection ; Life Sciences ; Medical Biochemistry ; Mice ; Mice, Inbred BALB C ; Molecular biology ; Molecular modelling ; Neoplasms, Experimental ; Oncology ; Oncolysis ; Oncolytic Virotherapy - methods ; Oncolytic Viruses - genetics ; Osteosarcoma ; Osteosarcoma - genetics ; Osteosarcoma - therapy ; Replication ; Therapeutic applications ; TNF-Related Apoptosis-Inducing Ligand - biosynthesis ; TNF-Related Apoptosis-Inducing Ligand - genetics ; TRAIL protein ; Tumors</subject><ispartof>Molecular and cellular biochemistry, 2012-05, Vol.364 (1-2), p.337-344</ispartof><rights>Springer Science+Business Media, LLC. 2012</rights><rights>COPYRIGHT 2012 Springer</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c504t-ae547c2e9481c2e1ac5bd99e5501e60b0adef7656022b37757eb697e5343b473</citedby><cites>FETCH-LOGICAL-c504t-ae547c2e9481c2e1ac5bd99e5501e60b0adef7656022b37757eb697e5343b473</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11010-012-1235-9$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11010-012-1235-9$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22354724$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chunbao, Li</creatorcontrib><creatorcontrib>Qianpeng, Cheng</creatorcontrib><creatorcontrib>Jia, Liu</creatorcontrib><creatorcontrib>Bin, Wang</creatorcontrib><creatorcontrib>Dongfeng, Chen</creatorcontrib><creatorcontrib>Yujie, Liu</creatorcontrib><title>Potent growth-inhibitory effect of TRAIL therapy mediated by double-regulated oncolytic adenovirus on osteosarcoma</title><title>Molecular and cellular biochemistry</title><addtitle>Mol Cell Biochem</addtitle><addtitle>Mol Cell Biochem</addtitle><description>Osteosarcoma (OS) severely threatens the health of young people and understanding on the molecular mechanisms of OS etiology enables gene therapy to become an effective therapeutic modality. However, insufficient expression level of genes using existing vectors limits the clinical application of gene therapy for OS. To solve the problem, we developed an oncolytic adenoviral vector, OAT, which can selectively and efficiently replicate in OS cells to enhance the expression of transferred genes. We demonstrated that OAT-mediated TRAIL expression is significantly elevated after infection of OS cells than replication-incompetent Ad5 vector. Increased antitumor capacity was observed in OS cells after OAT-TRAIL treatment both in vitro and in vivo. In normal cells, adenoviral replication, TRAIL expression and growth-inhibiting effect were quite limited when OAT-TRAIL was administrated, showing a high biosafety of this oncolytic adenoviral vector. Collectively, we generated an efficient and promising expression vector for OS gene therapy.</description><subject>Adenoviridae - genetics</subject><subject>Adenovirus</subject><subject>Adenoviruses</subject><subject>Animals</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biosafety</subject><subject>Bone cancer</subject><subject>Bone Neoplasms - genetics</subject><subject>Bone Neoplasms - therapy</subject><subject>Cardiology</subject><subject>Cell Line, Tumor</subject><subject>Development and progression</subject><subject>Etiology</subject><subject>Expression vectors</subject><subject>Fibroblasts - cytology</subject><subject>Gene expression</subject><subject>Gene therapy</subject><subject>Genetic engineering</subject><subject>Genetic Therapy - methods</subject><subject>Genetic Vectors</subject><subject>Green Fluorescent Proteins - genetics</subject><subject>Growth</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Infection</subject><subject>Life Sciences</subject><subject>Medical Biochemistry</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Molecular biology</subject><subject>Molecular modelling</subject><subject>Neoplasms, Experimental</subject><subject>Oncology</subject><subject>Oncolysis</subject><subject>Oncolytic Virotherapy - methods</subject><subject>Oncolytic Viruses - genetics</subject><subject>Osteosarcoma</subject><subject>Osteosarcoma - genetics</subject><subject>Osteosarcoma - therapy</subject><subject>Replication</subject><subject>Therapeutic applications</subject><subject>TNF-Related Apoptosis-Inducing Ligand - biosynthesis</subject><subject>TNF-Related Apoptosis-Inducing Ligand - genetics</subject><subject>TRAIL protein</subject><subject>Tumors</subject><issn>0300-8177</issn><issn>1573-4919</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kU9v1DAQxS0EokvhA3BBFly4uNhJHMfHVcWfSiuB0N4tx5nsukrixXaK8u2ZbQoIBPJhpPHvjZ_nEfJS8CvBuXqXhOCCMy4KJopSMv2IbIRUJau00I_Jhpecs0YodUGepXTLEeZCPCUXBdKVKqoNiV9ChinTQwzf85H56ehbn0NcKPQ9uExDT_dftzc7mo8Q7WmhI3TeZuhou9AuzO0ALMJhHu57YXJhWLJ31HYwhTsf54RNGlKGkGx0YbTPyZPeDglePNRLsv_wfn_9ie0-f7y53u6Yk7zKzAJadAXoqhFYhHWy7bQGKbmAmrccX-hVLWteFG2plFTQ1lqBLKuyrVR5Sd6uY08xfJshZTP65GAY7ARhTgZXVwne6LpB9PVf6G2Y44TmjC60QAP30JsVOtgBjJ_6kKN155lmW8qmwZ0LidTVPyg8HYzehQl6j_0_BGIVuBhSitCbU_SjjQsaNOeUzZqywZTNOWWjUfPqwe_cYhy_FD9jRaBYgYRX0wHi7w_9f-oPE1ixLQ</recordid><startdate>20120501</startdate><enddate>20120501</enddate><creator>Chunbao, Li</creator><creator>Qianpeng, Cheng</creator><creator>Jia, Liu</creator><creator>Bin, Wang</creator><creator>Dongfeng, Chen</creator><creator>Yujie, Liu</creator><general>Springer US</general><general>Springer</general><general>Springer Nature B.V</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>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7T5</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope></search><sort><creationdate>20120501</creationdate><title>Potent growth-inhibitory effect of TRAIL therapy mediated by double-regulated oncolytic adenovirus on osteosarcoma</title><author>Chunbao, Li ; Qianpeng, Cheng ; Jia, Liu ; Bin, Wang ; Dongfeng, Chen ; Yujie, Liu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c504t-ae547c2e9481c2e1ac5bd99e5501e60b0adef7656022b37757eb697e5343b473</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adenoviridae - 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However, insufficient expression level of genes using existing vectors limits the clinical application of gene therapy for OS. To solve the problem, we developed an oncolytic adenoviral vector, OAT, which can selectively and efficiently replicate in OS cells to enhance the expression of transferred genes. We demonstrated that OAT-mediated TRAIL expression is significantly elevated after infection of OS cells than replication-incompetent Ad5 vector. Increased antitumor capacity was observed in OS cells after OAT-TRAIL treatment both in vitro and in vivo. In normal cells, adenoviral replication, TRAIL expression and growth-inhibiting effect were quite limited when OAT-TRAIL was administrated, showing a high biosafety of this oncolytic adenoviral vector. Collectively, we generated an efficient and promising expression vector for OS gene therapy.</abstract><cop>Boston</cop><pub>Springer US</pub><pmid>22354724</pmid><doi>10.1007/s11010-012-1235-9</doi><tpages>8</tpages></addata></record> |
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| subjects | Adenoviridae - genetics Adenovirus Adenoviruses Animals Biochemistry Biomedical and Life Sciences Biosafety Bone cancer Bone Neoplasms - genetics Bone Neoplasms - therapy Cardiology Cell Line, Tumor Development and progression Etiology Expression vectors Fibroblasts - cytology Gene expression Gene therapy Genetic engineering Genetic Therapy - methods Genetic Vectors Green Fluorescent Proteins - genetics Growth Health aspects Humans Infection Life Sciences Medical Biochemistry Mice Mice, Inbred BALB C Molecular biology Molecular modelling Neoplasms, Experimental Oncology Oncolysis Oncolytic Virotherapy - methods Oncolytic Viruses - genetics Osteosarcoma Osteosarcoma - genetics Osteosarcoma - therapy Replication Therapeutic applications TNF-Related Apoptosis-Inducing Ligand - biosynthesis TNF-Related Apoptosis-Inducing Ligand - genetics TRAIL protein Tumors |
| title | Potent growth-inhibitory effect of TRAIL therapy mediated by double-regulated oncolytic adenovirus on osteosarcoma |
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