Enhanced sensitivity of hepatocellular carcinoma cells to chemotherapy with a Smac-armed oncolytic adenovirus
Aim： The aim of the present study was to further improve the therapeutic effects for human hepatocellular carcinoma （HCC） and reduce the damage in normal cells using a novel chemo-gene-virotherapeutic strategy. Methods： An oncolytic adenoviral vector （ZD55） similar to the typical oncolytic adenoviru...
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| Veröffentlicht in: | Acta pharmacologica Sinica 2007-12, Vol.28 (12), p.1996-2004 |
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| container_title | Acta pharmacologica Sinica |
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| creator | Pan, Qiu-wei Zhong, Su-yang Liu, Bi-sheng Liu, Jin Cai, Rong Wang, Yi-gang Liu, Xin-yuan Qian, Cheng |
| description | Aim： The aim of the present study was to further improve the therapeutic effects for human hepatocellular carcinoma （HCC） and reduce the damage in normal cells using a novel chemo-gene-virotherapeutic strategy. Methods： An oncolytic adenoviral vector （ZD55） similar to the typical oncolytic adenovirus ONYX-015, with a deletion of E1B-55K gene, was employed to express the second mitochon- dria-derived activator of caspases （Smac） protein by constructing a recombinant virus ZD55-Smac. The enhanced cytotoxicity of the combined treatment of ZD55- Smac with cisplatin or 5-fluorouracil （5-FU） was evaluated in several HCC cell lines. Moreover, the negative effects on normal cells have been tested in human normal liver cell lines L-02 and QSG-7701 cell lines by 3-（4,5-dimethylthiazol-2-yl）- 2,5-diphenyltetrazolium bromide assay and apoptotic cell staining. Results： According to our observation, ZD55-Smac is superior to ONYX-015 in sensitizing chemotherapy, ZD55-Smac used in conjunction with chemotherapy was found to exhibit obviously enhanced cytotoxicity in HCC cells, yet significantly abolished the negative toxicity in normal cells by utilizing the tumor selective replication vector and reducing the dosage. Conclusion： This chemo-gene-virotherapeutic （cisplatin or 5-FU＋ZD55-Smac） strategy is superior to the conventional chemo- gene or chemo-viro approach. |
| doi_str_mv | 10.1111/j.1745-7254.2007.00672.x |
| format | Article |
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Methods： An oncolytic adenoviral vector （ZD55） similar to the typical oncolytic adenovirus ONYX-015, with a deletion of E1B-55K gene, was employed to express the second mitochon- dria-derived activator of caspases （Smac） protein by constructing a recombinant virus ZD55-Smac. The enhanced cytotoxicity of the combined treatment of ZD55- Smac with cisplatin or 5-fluorouracil （5-FU） was evaluated in several HCC cell lines. Moreover, the negative effects on normal cells have been tested in human normal liver cell lines L-02 and QSG-7701 cell lines by 3-（4,5-dimethylthiazol-2-yl）- 2,5-diphenyltetrazolium bromide assay and apoptotic cell staining. Results： According to our observation, ZD55-Smac is superior to ONYX-015 in sensitizing chemotherapy, ZD55-Smac used in conjunction with chemotherapy was found to exhibit obviously enhanced cytotoxicity in HCC cells, yet significantly abolished the negative toxicity in normal cells by utilizing the tumor selective replication vector and reducing the dosage. Conclusion： This chemo-gene-virotherapeutic （cisplatin or 5-FU＋ZD55-Smac） strategy is superior to the conventional chemo- gene or chemo-viro approach.</description><identifier>ISSN: 1671-4083</identifier><identifier>EISSN: 1745-7254</identifier><identifier>DOI: 10.1111/j.1745-7254.2007.00672.x</identifier><identifier>PMID: 18031615</identifier><language>eng</language><publisher>United States: Nature Publishing Group</publisher><subject>Adenoviridae - genetics ; Adenovirus ; Antineoplastic Agents - therapeutic use ; Base Sequence ; Carcinoma, Hepatocellular - drug therapy ; Carcinoma, Hepatocellular - therapy ; Cell Line, Tumor ; DNA Primers ; Humans ; Liver Neoplasms - drug therapy ; Liver Neoplasms - therapy ; Oncolytic Virotherapy ; 抑制剂 ; 溶瘤腺病毒 ; 线粒体 ; 肝细胞癌</subject><ispartof>Acta pharmacologica Sinica, 2007-12, Vol.28 (12), p.1996-2004</ispartof><rights>Copyright Nature Publishing Group Dec 2007</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c449t-92f68a81d7ecd266ee870f3e2aa448d84a8cdd89314108dfb8fe156152f7174a3</citedby><cites>FETCH-LOGICAL-c449t-92f68a81d7ecd266ee870f3e2aa448d84a8cdd89314108dfb8fe156152f7174a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://image.cqvip.com/vip1000/qk/95561A/95561A.jpg</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18031615$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pan, Qiu-wei</creatorcontrib><creatorcontrib>Zhong, Su-yang</creatorcontrib><creatorcontrib>Liu, Bi-sheng</creatorcontrib><creatorcontrib>Liu, Jin</creatorcontrib><creatorcontrib>Cai, Rong</creatorcontrib><creatorcontrib>Wang, Yi-gang</creatorcontrib><creatorcontrib>Liu, Xin-yuan</creatorcontrib><creatorcontrib>Qian, Cheng</creatorcontrib><title>Enhanced sensitivity of hepatocellular carcinoma cells to chemotherapy with a Smac-armed oncolytic adenovirus</title><title>Acta pharmacologica Sinica</title><addtitle>Acta Pharmacologica Sinica</addtitle><description>Aim： The aim of the present study was to further improve the therapeutic effects for human hepatocellular carcinoma （HCC） and reduce the damage in normal cells using a novel chemo-gene-virotherapeutic strategy. 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Results： According to our observation, ZD55-Smac is superior to ONYX-015 in sensitizing chemotherapy, ZD55-Smac used in conjunction with chemotherapy was found to exhibit obviously enhanced cytotoxicity in HCC cells, yet significantly abolished the negative toxicity in normal cells by utilizing the tumor selective replication vector and reducing the dosage. 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Methods： An oncolytic adenoviral vector （ZD55） similar to the typical oncolytic adenovirus ONYX-015, with a deletion of E1B-55K gene, was employed to express the second mitochon- dria-derived activator of caspases （Smac） protein by constructing a recombinant virus ZD55-Smac. The enhanced cytotoxicity of the combined treatment of ZD55- Smac with cisplatin or 5-fluorouracil （5-FU） was evaluated in several HCC cell lines. Moreover, the negative effects on normal cells have been tested in human normal liver cell lines L-02 and QSG-7701 cell lines by 3-（4,5-dimethylthiazol-2-yl）- 2,5-diphenyltetrazolium bromide assay and apoptotic cell staining. Results： According to our observation, ZD55-Smac is superior to ONYX-015 in sensitizing chemotherapy, ZD55-Smac used in conjunction with chemotherapy was found to exhibit obviously enhanced cytotoxicity in HCC cells, yet significantly abolished the negative toxicity in normal cells by utilizing the tumor selective replication vector and reducing the dosage. Conclusion： This chemo-gene-virotherapeutic （cisplatin or 5-FU＋ZD55-Smac） strategy is superior to the conventional chemo- gene or chemo-viro approach.</abstract><cop>United States</cop><pub>Nature Publishing Group</pub><pmid>18031615</pmid><doi>10.1111/j.1745-7254.2007.00672.x</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Acta pharmacologica Sinica, 2007-12, Vol.28 (12), p.1996-2004 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Adenoviridae - genetics Adenovirus Antineoplastic Agents - therapeutic use Base Sequence Carcinoma, Hepatocellular - drug therapy Carcinoma, Hepatocellular - therapy Cell Line, Tumor DNA Primers Humans Liver Neoplasms - drug therapy Liver Neoplasms - therapy Oncolytic Virotherapy 抑制剂 溶瘤腺病毒 线粒体 肝细胞癌 |
| title | Enhanced sensitivity of hepatocellular carcinoma cells to chemotherapy with a Smac-armed oncolytic adenovirus |
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