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Suppression of bone metastatic castration-resistant prostate cancer cell growth by a suicide gene delivered by JC polyomavirus-like particles

Gene Therapy volume 30, pages 534–537 (2023)Cite this article

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Abstract

Prostate cancer is one of the most common cancers in men. The heterogeneity and mutations exhibited by prostate cancer cells often results in the progression to incurable metastatic castration-resistant prostate cancer (mCRPC). Our previous investigations demonstrated that the virus-like particles (VLPs) of JC polyomavirus (JCPyV) can deliver exogenous genes to prostate cancer cells for expression. JCPyV VLPs packaging pPSAtk (PSAtk-VLPs) possess the ability to transcriptionally target and selectively induce cytotoxicity in prostate cancer cells in vitro and in vivo, as pPSAtk can only express the thymidine kinase gene, a suicide gene, in androgen receptor-positive cells. To further investigate whether PSAtk-VLPs inhibit the growth of metastasized prostate cancer cells, we established an animal model of bone-metastatic prostate cancer to compare PSAtk-VLPs with leuprorelin acetate and enzalutamide, hormonal agents commonly used in clinical settings, and investigated the effectiveness of PSAtk-VLPs. In the present study, we observed that PSAtk-VLPs effectively inhibited the growth of prostate cancer cells that had metastasized to the bone in the metastatic animal model. In addition, PSAtk-VLPs showed a higher effectiveness than hormone therapy in this animal model study. These results suggest that PSAtk-VLPs may serve as a treatment option for mCRPC therapy in the future.

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Fig. 1: Determination of prostate cancer cell growth in the bone.

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Acknowledgements

IVIS Lumina II was performed in the Instrument Center of Chung Shan Medical University, which is supported by National Science Council, Ministry of Education and Chung Shan Medical University.

Funding

This research was funded by the Ministry of Science and Technology [grant number MOST 106-2320-B-194-002-MY3], Taiwan.

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Author notes

  1. These authors contributed equally: Cheng-Huang Shen, Mien-Chun Lin.

Authors and Affiliations

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

    Cheng-Huang Shen & Mien-Chun Lin

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

    Chiung-Yao Fang

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

    Pei-Lain Chen

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

    Chih-Chieh Chou & Deching Chang

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

    Chun-Liang Tung

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

    Chun-Nun Chao

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

    Meilin Wang

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  1. Cheng-Huang Shen
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  8. Deching Chang
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Contributions

Experiments performing, manuscript writing: M-CL, C-HS, and MW. Review, and/or revision of the manuscript, Data collection and data analysis: M-CL, C-HS, C-YF, P-LC, C-CC, C-LT, and C-NC Study design, organization, and data analysis: DC and MW.

Corresponding authors

Correspondence to Deching Chang or Meilin Wang.

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Shen, CH., Lin, MC., Fang, CY. et al. Suppression of bone metastatic castration-resistant prostate cancer cell growth by a suicide gene delivered by JC polyomavirus-like particles. Gene Ther 30, 534–537 (2023). https://doi.org/10.1038/s41434-021-00280-8

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