Treatment of pancreatic cancer using an oncolytic virus harboring the lipocalin-2 gene

Authors

  • Bin Xu MD,

    Corresponding author
    1. Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
    • Bin Xu, Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai 200072, China

      Xin-yuan Liu, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China

      Xin-yu Qin, Department of General Surgery, Zhong Shan Hospital, Fudan University, Shanghai 200032, China, China

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    • Fax: (011) 86-21-54921126

  • Wen-yan Zheng MM,

    1. Department of Surgical Intensive Care Unit, Zhong Shan Hospital, Fudan University, Shanghai, China
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  • Da-yong Jin MD,

    1. Department of General Surgery, Zhong Shan Hospital, Fudan University, Shanghai, China
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  • Dan-song Wang MD,

    1. Department of General Surgery, Zhong Shan Hospital, Fudan University, Shanghai, China
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    • Bin Xu and Dan-song Wang contributed equally to this article.

  • Xin-yuan Liu PhD,

    Corresponding author
    1. Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    • Bin Xu, Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai 200072, China

      Xin-yuan Liu, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China

      Xin-yu Qin, Department of General Surgery, Zhong Shan Hospital, Fudan University, Shanghai 200032, China, China

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    • Fax: (011) 86-21-54921126

  • Xin-yu Qin MD

    Corresponding author
    1. Department of General Surgery, Zhong Shan Hospital, Fudan University, Shanghai, China
    • Bin Xu, Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai 200072, China

      Xin-yuan Liu, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China

      Xin-yu Qin, Department of General Surgery, Zhong Shan Hospital, Fudan University, Shanghai 200032, China, China

    Search for more papers by this author
    • Fax: (011) 86 21 64037224


Abstract

BACKGROUND:

The 5-year survival rate for patients with pancreatic cancer is <5%, and it is always resistant to the current chemoradiotherapy. Therefore, new, effective agents for the treatment of pancreatic cancer are urgently needed. The promising strategy of cancer-targeting gene virotherapy (CTGVT) has demonstrated great anticancer potential. The objective of the current study was to determine whether 1 CTGVT approach, oncolytic virus (OV)-harboring lipocalin-2, is capable of treating pancreatic cancer.

METHODS:

Tissue microarrays were constructed to detect the expression of lipocalin-2 in 60 specimens of pancreatic adenocarcinoma. The clinical significance of lipocalin-2 was investigated in an analysis of correlations between lipocalin-2 expression and matched clinical characteristics. A lipocalin-2–expressing OV, ZD55-lipocalin-2, was constructed by deleting the adenoviral protein E1B55kD. The antitumor efficacy and mechanisms of the OV were investigated in pancreatic cancer cells with v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in vitro and in vivo.

RESULTS:

Lipocalin-2 expression was correlated with a good prognosis in patients with pancreatic adenocarcinoma. ZD55-lipocalin-2 dramatically inhibited the growth of pancreatic cancer in vitro and in vivo by inducing cytolysis and caspase-dependent apoptosis.

CONCLUSIONS:

Higher lipocalin-2 expression predicted a better prognosis in patients with pancreatic cancer. The results indicated that ZD55-lipocalin-2, which specifically expressed higher levels of lipocalin-2 in tumor cells, may serve as a potent anticancer drug for pancreatic cancer therapy, especially for patients who have pancreatic adenocarcinoma with KRAS mutations. Cancer 2012. © 2012 American Cancer Society.

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