Bastide C, Maroc N, Bladou F, Hassoun J, Maitland N, Mannoni P, Bagnis C
Institut Paoli-Calmettes, Marseille, France.
Prostate Cancer Prostatic Dis. 2003;6(3):228-34. doi: 10.1038/sj.pcan.4500668.
In a preclinical model for prostate cancer gene therapy, we have tested lentiviral vectors as a practical possibility for the transfer and long-term expression of the EGFP gene both in vitro and in vivo. The human prostate cancer cell lines DU145 and PC3 were transduced using experimental conditions which permitted analysis of the expression from a single proviral vector per cell. The transduced cells stably expressed the EGFP transgene for 4 months. After injection of the transduced cell populations into Nod-SCID mice a decrease in EGFP was only observed in a minority of cases, while the majority of tumors maintained transgene expression at in vitro levels. In vivo injection of viral vector preparations directly into pre-established subcutaneous or orthotopic tumor masses, obtained by implantation of untransduced PC3 and DU145 cells led to a high transduction efficiency. While the efficiency of direct intratumoral transduction was proportional to the dose of virus injected, the results indicated some technical limitations inherent in these approaches to prostate cancer gene therapy.
在前列腺癌基因治疗的临床前模型中，我们测试了慢病毒载体作为在体外和体内转移及长期表达EGFP基因的一种实际可能性。使用允许分析每个细胞单个前病毒载体表达的实验条件转导人前列腺癌细胞系DU145和PC3。转导的细胞稳定表达EGFP转基因达4个月。将转导的细胞群体注射到Nod-SCID小鼠体内后，仅在少数情况下观察到EGFP减少，而大多数肿瘤维持转基因表达在体外水平。将病毒载体制剂直接体内注射到通过植入未转导的PC3和DU145细胞获得的预先建立的皮下或原位肿瘤块中，导致了高转导效率。虽然直接瘤内转导的效率与注射的病毒剂量成正比，但结果表明这些前列腺癌基因治疗方法存在一些固有的技术限制。
