论文部分内容阅读
Aim:The aim of the present study was to further improve the therapeutic effectsfor human hepatocellular carcinoma (HCC) and reduce the damage in normal cellsusing a novel chemo-gene-virotherapeutic strategy.Methods:An oncolyticadenoviral vector (ZD55) similar to the typical oncolytic adenovirus ONYX-015,with a deletion of ElB-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 celllines.Moreover,the negative effects on normal cells have been tested in humannormal 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 sensitizingchemotherapy,ZD55-Smac used in conjunction with chemotherapy was found toexhibit obviously enhanced cytotoxicity in HCC cells,yet significantly abolishedthe negative toxicity in normal cells by utilizing the tumor selective replicationvector 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.
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 oncolyticadenoviral vector (ZD55) similar to the typical oncolytic adenovirus ONYX-015, with a deletion of ElB-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 ZO55-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 humannormal 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 t oexhibitarently 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. Confclusion: This chemo-gene-virotherapeutic (cisplatin or 5-FU + ZD55- Smac) strategy is superior to the conventional chemo-gene or chemo-viro approach.