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

Qiu Wei Pan, Su Yang Zhong, Bi Sheng Liu, Jin Liu, Rong Cai, Yi Gang Wang, Xin Yuan Liu*, Cheng Qian*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

25 Citations (Scopus)
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Abstract

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 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. Conclusion: This chemo-gene-virotherapeutic (cisplatin or 5-FU+ZD55-Smac) strategy is superior to the conventional chemo-gene or chemo-viro approach.

Original languageEnglish
Pages (from-to)1996-2004
Number of pages9
JournalActa Pharmacologica Sinica
Volume28
Issue number12
DOIs
Publication statusPublished - 1 Dec 2007
Externally publishedYes

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