Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Int J Cancer. 2010 Aug 1;127(3):707-17. doi: 10.1002/ijc.25069.
Prostate cancer (PCa) is the second leading cause of cancer-related deaths in Western male population. Previous studies have demonstrated that differential display code 3 (DD3 or DD3(PCA3)) is one of the most PCa-specific genes; therefore, it has been used as a clinical diagnostic marker for PCa. In this study, we constructed an oncolytic adenovirus Ad.DD3-E1A by using the minimal DD3 promoter to replace the native viral promoter of E1A gene. In addition, Ad.DD3-E1A was armed with therapeutic gene IL-24 to enhance its antitumor activity. The resulting adenovirus, Ad.DD3-E1A-IL-24, demonstrated PCa specificity and excellent antitumor effect. Further analyses on its antitumor mechanism revealed that it has the capacity to induce apoptosis in PCa cells and inhibit angiogenesis. These results suggest that Ad.DD3-E1A-IL-24 is a promising antitumor agent that may be able to be used in the future as a treatment for PCa.
前列腺癌（PCa）是西方男性人群癌症相关死亡的第二大主要原因。先前的研究表明，差异显示代码 3（DD3 或 DD3(PCA3)）是最具 PCa 特异性的基因之一；因此，它已被用作 PCa 的临床诊断标志物。在这项研究中，我们构建了一种溶瘤腺病毒 Ad.DD3-E1A，使用最小的 DD3 启动子取代 E1A 基因的天然病毒启动子。此外，Ad.DD3-E1A 被武装了治疗基因 IL-24，以增强其抗肿瘤活性。所得腺病毒 Ad.DD3-E1A-IL-24 表现出 PCa 特异性和优异的抗肿瘤作用。对其抗肿瘤机制的进一步分析表明，它具有诱导 PCa 细胞凋亡和抑制血管生成的能力。这些结果表明，Ad.DD3-E1A-IL-24 是一种有前途的抗肿瘤药物，将来可能能够用于治疗 PCa。
