Shirakawa T, Gotoh A, Gardner T A, Kao C, Zhang Z J, Matsubara S, Wada Y, Hinata N, Fujisawa M, Hanioka K, Matsuo M, Kamidono S
Department of Urology, Kobe University School of Medicine, Japan.
J Gene Med. 2000 Nov-Dec;2(6):426-32. doi: 10.1002/1521-2254(200011/12)2:6<426::AID-JGM140>3.0.CO;2-2.
Benign prostatic hyperplasia (BPH) is the most common proliferative disease affecting men. Numerous minimally invasive technologies are being developed or are currently in use to obviate the need for transurethral surgery. The goal of the present study was to develop a novel molecular based approach for the treatment of BPH using recombinant p53 adenoviral vector. The over-expression of wt-p53 can cause cell apoptosis or cell growth arrest, thus preventing the uncontrolled cell proliferation underlying BPH pathophysiology.
Ad-CMV-p53, a replication-deficient recombinant adenovirus containing cytomegalovirus promoter driving p53 gene, was used. Human prostate stromal (PS) cells were evaluated for apoptosis (TUNEL assay), mRNA levels of key cell cycle regulators influencing apoptosis (p-53, Bax and Bcl-2) using quantitative RT-PCR and cytotoxicity after Ad-CMV-p53. Ad-CMV-p53 was unilaterally injected into rat ventral prostates and growth inhibition was measured by prostate weight 3 weeks after injection.
In vitro exposure to Ad-CMV-p53 significantly inhibited the proliferation of PS cells, induced mRNA over-expression of both wt-p53 and Bax, and increased the proportion of apoptotic cells. A 30% decrease in average prostate weight was demonstrated in rodents after Ad-CMV-p53 injection.
The results suggest that further investigation of molecular gene therapy with recombinant wt-p53 adenovirus for the treatment of BPH is warranted.
良性前列腺增生（BPH）是影响男性的最常见增殖性疾病。目前正在开发或已在使用多种微创技术，以避免经尿道手术的需要。本研究的目的是开发一种基于重组p53腺病毒载体治疗BPH的新型分子方法。野生型p53的过表达可导致细胞凋亡或细胞生长停滞，从而防止BPH病理生理学中不受控制的细胞增殖。
使用Ad-CMV-p53，一种含有驱动p53基因的巨细胞病毒启动子的复制缺陷型重组腺病毒。通过TUNEL法评估人前列腺基质（PS）细胞的凋亡情况，使用定量RT-PCR检测影响凋亡的关键细胞周期调节因子（p-53、Bax和Bcl-2）的mRNA水平，并检测Ad-CMV-p53处理后的细胞毒性。将Ad-CMV-p53单侧注射到大鼠腹侧前列腺中，注射3周后通过前列腺重量测量生长抑制情况。
体外暴露于Ad-CMV-p53可显著抑制PS细胞的增殖，诱导野生型p53和Bax的mRNA过表达，并增加凋亡细胞的比例。Ad-CMV-p53注射后，啮齿动物的平均前列腺重量降低了30%。
结果表明，有必要进一步研究重组野生型p53腺病毒用于治疗BPH的分子基因疗法。
