攝護腺癌標靶基因治療之研究
沈正煌1、林昌德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 targeted gene therapy for prostate cancer
Cheng-Huang Shen1, Chang-Te Lin1, 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 prostate cancer cell was assayed with CCK-8 to assess the tissue-specific cytotoxicity conferred by pPSA-tk to JCPyV VLPs (PSAtk-VLPs).
Results:
Results show that the tissue specificity conferred by the PSA promoter and the viability of prostate cancer cells treated with PSAtk-VLPs in combination with gancyclovir (GCV) reduced by 50%, relative to the controls.
Conclusion:
The results demonstrate the possibility of developing pPSA-tk-transducing JCPyV VLPs as a targeted prostate cancer therapy.