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Gene Therapy of Lung Adenocarcinoma using Herpes Virus Expressing a Fusogenic Membrane Glycoprotein

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Abstract

The aim of this study is to observe the in vitro-targeted destruction of lung adenocarcinoma using recombinant Type I herpes simplex virus (HSV-I)-mediated gibbon ape leukemia virus envelope glycoprotein (GALV.fus), controlled by UL38 promoter and cytomegalovirus promoter (CMVP). A recombinant HSV-I plasmid encoding the GALV.fus was transfected into green monkey kidney cells, the lung adenocarcinoma line A549, and the human fetal fibroblast cell line HFL-I GNHu5 in various doses. The effects and expression of in vitro GALV.fus were observed using an inverted microscope. Enhanced green fluorescence protein expression served as the contro1 for GALV.fus. Recombinant HSV-I virus was produced. Fusogenic recombinant virus infection led to cell fusions in A549 in a dose-dependent manner. Nonfusogenic viruses only produced conventional cytotoxic effects. Recombinant HSV-I with the CMVP initiated cell fusions in HFL-1 GNHu5 cells with arrested cell cycles or as quiescence. HSV-I regulated by UL38p caused cell fusion only in growing cells. Protein expression of GALV.fus was confirmed by Western Blot in infected A549 and HFL-1 GNHu5. Delivery and tumor-specific expression of GALV.fus gene can selectively and safely target lung cancer in vitro, and may prove to be a novel gene therapy for lung cancer.

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References

  1. Kamlah, F., Eul, B. G., Li, S., Lang, N., Marsh, L. M., Seeger, W., et al. (2009). Intravenous injection of siRNA directed against hypoxia-inducible factors prolongs survival in a lewis lung carcinoma cancer model. Cancer Gene therapy, 16, 195–205.

    CAS  Google Scholar 

  2. Qi, R., Ma, Y., & Liu, Z. (2007). The Pro206Pro and Gln632Gln polymorphisms in DNA repair gene XRCC1 and genetic susceptibility to lung cancer in the Chinese population. Chinese Journal of Clinical Oncology, 34, 4.

    Google Scholar 

  3. Nakamori, M., Fu, X., Pettaway, C. A., & Zhang, X. (2004). Potent antitumor activity after systemic delivery of a doubly fusogenic oncolytic herpes simplex virus against metastatic prostate cancer. The Prostate, 60, 53–60. 2004.

    Article  CAS  PubMed  Google Scholar 

  4. Fu, X., Tao, L., Li, M., Fisher, W. E., & Zhang, X. (2006). Effective treatment of pancreatic cancer xenografts with a conditionally replicating virus derived from type 2 herpes simplex virus. Clinical Cancer Research, 12, 3152–3157. 2006.

    Article  CAS  PubMed  Google Scholar 

  5. Burton, E. A., Wechuck, J. B., Wendell, S. K., Goins, W. F., Fink, D. J., & Glorioso, J. C. (2001). Multiple applications for replication-defective herpes simplex virus vectors. Stem Cells, 19, 358–377. 2001.

    Article  CAS  PubMed  Google Scholar 

  6. Tan, L., Jia, H., Liu, R., Wu, J., Han, H., Zuo, Y., et al. (2009). Inhibition of NF-kappaB in fusogenic membrane glycoprotein causing HL-60 cell death: implications for acute myeloid leukemia. Cancer Letters, 273, 114–121. 2009.

    Article  CAS  PubMed  Google Scholar 

  7. Ji, K., Wang, X., & Xu, A. (2008). Targeting expression of TAT-EGFP driven by the prostate specific antigen promoter. Journal of Shandong University: Health Sciences, 46, 5.

    Google Scholar 

  8. Jones, C., Inman, M., Peng, W., Henderson, G., Doster, A., Perng, G. C., et al. (2005). The herpes simplex virus type 1 locus that encodes the latency-associated transcript enhances the frequency of encephalitis in male BALB/c mice. Journal of virology, 79, 14465–14469.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Martin, E. T., Koelle, D. M., Byrd, B., Huang, M. L., Vieira, J., Corey, L., et al. (2006). Sequence-based methods for identifying epidemiologically linked herpes simplex virus type 2 strains. Journal of Clinical Microbiology, 44, 2541–2546.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Javanmoghadam-Kamrani, S., & Keyomarsi, K. (2008). Synchronization of the cell cycle using lovastatin. Cell Cycle, 15, 7.

    Google Scholar 

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Acknowledgments

This study was supported by the National Natural Sciences Foundation of China (Grant No. 30471984) , the Foundation of Bureau of Public Health of Chongqing (Grants 06-2-001 and 2010-2-127), and the project Innovation of Science and Technology, Chongqing Science and Technology Commission (Project No. cstc2013jcyjA10108).

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Authors and Affiliations

  1. Department of Cardiothoracic Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China

    Bing Zhu, Yue-quan Jiang, Shi-feng Chen & Xin-ping Fu

  2. The Central Laboratory, The Sixth Hospital of Handan, Handan, 056000, China

    Jian-ru Yang

Authors
  1. Bing Zhu
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  2. Jian-ru Yang
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  3. Yue-quan Jiang
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  4. Shi-feng Chen
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  5. Xin-ping Fu
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Correspondence to Bing Zhu.

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Zhu, B., Yang, Jr., Jiang, Yq. et al. Gene Therapy of Lung Adenocarcinoma using Herpes Virus Expressing a Fusogenic Membrane Glycoprotein. Cell Biochem Biophys 69, 583–587 (2014). https://doi.org/10.1007/s12013-014-9836-4

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  • DOI: https://doi.org/10.1007/s12013-014-9836-4

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