Enhanced sensitivity of hepatocellular carcinoma cells to chemotherapy with a Smac-armed oncolytic adenovirus.
OBJECTIVE
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 mitochondria-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.


CONCLUSIONS
This chemo-gene-virotherapeutic (cisplatin or 5-FU+ZD55-Smac) strategy is superior to the conventional chemo-gene or chemo-viro approach.
Pan
Qiu-wei
QW
Xin Yuan Institute of Medicine and Biotechnology, Life Science College, Zhejiang Sci-Tech University, Hangzhou 310018, China.
Zhong
Su-yang
SY
Liu
Bi-sheng
BS
Liu
Jin
J
Cai
Rong
R
Wang
Yi-gang
YG
Liu
Xin-yuan
XY
Qian
Cheng
C
D000256:Adenoviridae / Q000235:genetics*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000628:therapy; D045744:Cell Line, Tumor; D017931:DNA Primers; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000628:therapy; D050130:Oncolytic Virotherapy
D000970:Antineoplastic Agents; D017931:DNA Primers