利用JC類病毒殼體攜帶自殺基因作為攝護腺癌標靶基因治療之研究
沈正煌1、周詠欽1、賴韋宏1、林勉君1,2、張德卿2
1嘉義基督教醫院泌尿外科; 2國立中正大學分子生物研究所
Investigation of target gene therapy for prostate cancer by the JC virus-like particles delivering a suicide gene expressed by PSA promoter
Cheng-Huang Shen1, Yeong-Chin Jou1, Wei-Hong Lai1, Mien-Chun Lin 1,2, Deching Chang2
1Department of Urology, Chiayi Christian Hospital, Chiayi, Taiwan; 2National Chung Cheng University, Chiayi, Taiwan.
Purpose:
To develop non–androgen deprivation approaches for castration-resistant prostate cancer treatment, the JC polyomavirus virus-like particle (JCPyV VLP), was used as a vector to deliver a suicide gene driven by prostate-specific (PSA) promoter for targeted gene therapy of androgen receptor positive (AR+) prostate cancer.
Materials and Methods:
A prostate specific expression plasmid for a reporter gene, the green fluorescence protein gene (pPSA-gfp), and a suicide gene, the thymidine kinase gene (pPSA-tk), were constructed. JCPyV VLP was employed at as a delivery vehicle to transduce the plasmids into human prostate cancer cells. The specific expression of pPSA-gfp in AR+ prostate cancer cells was analyzed by fluorescence microscopy. The tissue-specific cytotoxicity conferred by pPSA-tk to JCPyV VLPs (PSAtk-VLPs) was confirmed in vitro and in a xenograft mouse model.
Results:
Results show that treatment with PSAtk-VLPs in combination with gancyclovir (GCV) specific reduced the viability of AR+ prostate cancer cells in vitro, and inhibited the tumor growth in xenograft mouse model.
Conclusion:
The results demonstrate the possibility of developing pPSA-tk-transducing JCPyV VLPs as a targeted prostate cancer therapy.