Inhibition of orthotopic castration-resistant prostate cancer growth and metastasis in mice by JC VLPs carrying a suicide gene driven by the PSA promoter.
Cancer Gene Ther
; 31(2): 250-258, 2024 02.
Article
em En
| MEDLINE
| ID: mdl-38072969
ABSTRACT
Metastatic castration-resistant prostate cancer (mCRPC) is challenging to treat. Virus-like particles (VLPs), originating from JC polyomavirus (JCPyV) and carrying a suicide gene driven by the PSA promoter (PSAtk-VLPs), can inhibit tumor growth in animal models of human prostate cancer. However, the efficacy of suppression of orthotopic PCa growth and metastasis by PSAtk-VLPs remains undetermined. Here, we established an iRFP stable expression CRPC cell line suitable for deep-tissue observation using fluorescence molecular tomography (FMT). These cells were implanted into murine prostate tissue, and PSAtk-VLPs were systemically administered via the tail vein along with the prodrug ganciclovir (GCV), allowing for the real-time observation of orthotopic prostate tumor growth and CRPC tumor metastasis. Our findings demonstrated that systemic PSAtk-VLPs administration with GCV and subsequent FMT scanning facilitated real-time observation of the suppressed growth in mouse iRFP CRPC orthotopic tumors, which further revealed a notable metastasis rate reduction. Systemic PSAtk-VLPs and GCV administration effectively inhibited orthotopic prostate cancer growth and metastasis. These findings suggest the potential of JCPyV VLPs as a promising vector for mCRPC gene therapy. Conclusively, systemically administered JCPyV VLPs carrying a tissue-specific promoter, JCPyV VLPs can protect genes within the bloodstream to be specifically expressed in specific organs.
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Base de dados:
MEDLINE
Assunto principal:
Vírus JC
/
Neoplasias de Próstata Resistentes à Castração
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article