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Gene therapy for castration-resistant prostate cancer cells using JC polyomavirus-like particles packaged with a PSA promoter driven-suicide gene

Cancer Gene Therapy volume 26, pages 208–215 (2019)Cite this article

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Abstract

Prostate cancer is the second most common cancer in men globally. Prostate cancer patients at advanced stages are usually treated with androgen deprivation therapy (ADT). However, with disease progression, it often becomes the incurable castration-resistant prostate cancer (CRPC). JC polyomavirus (JCPyV) is a human DNA virus. Its virus-like particles (VLPs) exhibit similar tropism to native virions and they are capable of delivering exogenous genes to the target cells for expression. JCPyV has been detected in prostate cells; therefore, prostate cancer cells may be susceptible to JCPyV infection and JCPyV VLPs may be used as a vector for gene therapy against prostate cancer. Here we constructed a plasmid (pPSAtk) that allows expression of the thymidine kinase suicide gene only in androgen receptor (AR) positive prostate cancer cells using the prostate-specific antigen (PSA) promoter, and used JCPyV VLPs as a vector to carry pPSAtk (PSAtk-VLPs) for transcriptional targeting in prostate cancer cells. In this study, we found that PSAtk-VLPs could only kill AR-positive CRPC 22Rv1 cells in vitro and inhibit the growth of tumor nodules in the xenograft mouse model. Our results reveal that PSAtk-VLPs could potentially be used as a new option for treating CRPC patients in the future.

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Acknowledgements

This research was supported by the Ministry of Science and Technology [grant number MOST 106-2320-B-194-002-MY3], Taiwan; and through Ditmanson Medical Foundation Chiayi Christian Hospital [grant number R104-023].

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Authors and Affiliations

  1. Institute of Molecular Biology, National Chung Cheng University, Chiayi, Taiwan

    Mien-Chun Lin, Ming-Chieh Chou & Deching Chang

  2. Department of Urology, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan

    Mien-Chun Lin & Cheng-Huang Shen

  3. Department of Microbiology and Immunology, School of Medicine, Chung-Shan Medical University and Clinical Laboratory, Chung-Shan Medical University Hospital, Taichung, Taiwan

    Meilin Wang

  4. Department of Pediatrics, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan

    Ming-Chieh Chou & Chun-Nun Chao

  5. Department of Medical Research, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan

    Chiung-Yao Fang

  6. Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taichung, Taiwan

    Pei-Lain Chen

  7. Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan

    Cheng-Huang Shen

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  1. Mien-Chun Lin
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Correspondence to Deching Chang or Cheng-Huang Shen.

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Lin, MC., Wang, M., Chou, MC. et al. Gene therapy for castration-resistant prostate cancer cells using JC polyomavirus-like particles packaged with a PSA promoter driven-suicide gene. Cancer Gene Ther 26, 208–215 (2019). https://doi.org/10.1038/s41417-019-0083-0

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