Abstract
Previous studies have shown that the application of Ad/AFPtBid significantly and specifically killed hepatocellular carcinoma (HCC) cells in culture and subcutaneously implanted in mice. This study was to test the therapeutic efficacy of Ad/AFPtBid in an orthotopic hepatic tumor model. Four weeks after implantation of tumor cells into the liver, nude mice were treated with Ad/AFPtBid alone or in combination with 5-fluorouracil (5-FU). Serum α-fetoprotein (AFP) was measured as a marker for tumor progression. The results showed that Ad/AFPtBid significantly inhibited Hep3B tumor growth. Ad/AFPtBid and 5-FU in combination was more effective than either agent alone. Tumor tissues of Ad/AFPtBid alone or combination treatment groups showed a decrease in cells positive for proliferation cell nuclear antigen, but an increase in apoptosis. Ad/AFPtBid did not suppress the hepatic tumor formed by non-AFP-producing hepatoma SK-HEP-1 cells or colorectal adenocarcinoma DLD-1 cells. The survival rate was higher in mice treated with Ad/AFPtBid plus 5-FU than those treated with either agent alone. No acute toxic effect was observed in mice receiving Ad/AFPtBid. Collectively, Ad/AFPtBid can specifically target and effectively suppress the AFP-producing orthotopic liver tumor in mice without obvious toxicity, indicating that it is a promising tool in combination with chemotherapeutic agents for treatment of AFP-producing HCC.
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Acknowledgements
This work was supported by Research Grants Council of the Hong Kong Special Administrative Region (No. CUHK 4534/06M). We are grateful to Ji Miao and Suk Ying Chun (Department of Surgery, The Chinese University of Hong Kong) for their help in providing adenovirus for the experiments.
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Ma, SH., Chen, G., Yip, J. et al. Therapeutic effect of α-fetoprotein promoter-mediated tBid and chemotherapeutic agents on orthotopic liver tumor in mice. Gene Ther 17, 905–912 (2010). https://doi.org/10.1038/gt.2010.34
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DOI: https://doi.org/10.1038/gt.2010.34
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