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Cancer targeting gene-viro-therapy for pancreatic cancer using oncolytic adenovirus ZD55-IL-24 in immune-competent mice

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Abstract

Cancer targeting gene-viro-therapy (CTGVT) may prove to be an effective treatment for pancreatic cancer (PC). This study was intended to explore the anti-tumor effect of ZD55-IL-24 (oncolytic adenovirus ZD55 harboring IL-24) on PC in immune-competent mice. The expression of gene harbored by oncolytic adenovirus ZD55 in PC cells was detected by reporter-gene assays. The in vitro anti PC ability of ZD55-IL-24 was tested by MTT, crystal violet staining and apoptosis assays. The in vivo anti PC effect of ZD55-IL-24 was further observed in an immune-competent mice model by detecting anti-tumor immunity and induction of apoptosis. The expression of gene harbored by ZD55 in PC cells was significantly higher than that harbored by the replicated-deficient adenovirus, and the amount of gene expression was time-dependent and dose-dependent. Both ZD55-IL-24 and ZD55 inhibited PC cells growth, but the anti-tumor effect of ZD55-IL-24 was significantly stronger than that of ZD55, and the ability of ZD55-IL-24 in inducing PC apoptosis was significantly stronger than that of ZD55. The tumor-forming rate of group ZD55-IL-24 was the lowest, and the tumor-growing rate was also significantly lower than that of group ZD55 in immune-competent PC models. Moreover, ZD55-IL-24 mediated more anti-cancer immunity effects by induction of stronger T-lymphocytes response to PC cells, higher levels of γ-IFN and IL-6 cytokines. ZD55-IL-24-mediated CTGVT could inhibit PC growth not only by inducing oncolysis and apoptosis but enhancing the anti-cancer immune effects by inducing T cell response to PC and up-regulating γ-IFN and IL-6 cytokine in immune-competent mice. This may serve as a candidate therapeutic approach for the treatment of PC.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (81001007, 81270003, 31100639); the Program for Young Excellent Talents in Tongji University (2008KJ060); and Youth Fund of Shanghai 10th People’s Hospital (10RQ105).

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Authors and Affiliations

  1. Department of Anesthesiology and SICU, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Kongjiang Road 1665, Shanghai, 200092, China

    Bin He

  2. Department of Hepatobiliary-Pancreatic Surgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, China

    Bin He & Bin Xu

  3. Department of General Surgery, 6th People’s Hospital of Shanghai, Shanghai Jiaotong University, Shanghai, 200233, China

    Xiuyan Huang

  4. Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai, 200031, China

    Xinyuan Liu

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  1. Bin He
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  2. Xiuyan Huang
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  3. Xinyuan Liu
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  4. Bin Xu
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Corresponding authors

Correspondence to Bin He or Bin Xu.

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Bin He and Xiuyan Huang contributed equally to this work.

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He, B., Huang, X., Liu, X. et al. Cancer targeting gene-viro-therapy for pancreatic cancer using oncolytic adenovirus ZD55-IL-24 in immune-competent mice. Mol Biol Rep 40, 5397–5405 (2013). https://doi.org/10.1007/s11033-013-2638-8

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  • DOI: https://doi.org/10.1007/s11033-013-2638-8

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