Laboratory of Cell and Gene Therapy Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Japan.
Anticancer Res. 2012 Sep;32(9):3743-7.
Adenovirus vectors have been utilized for cancer gene therapies. The present study examined the oncolytic effects of adenovirus type 5 (Ad5) and fiber-substituted conditionally replicating adenovirus (CRAD) Ad5/F35 vectors on the human malignant mesothelioma cells MSTO-211H, NCI-H28, NCI-H2052, and NCI-H2452 cells.
For the adenovirus, the first mRNA/protein to be made (~1 h after infection) is E1A. Ad5F35 and Ad5 CRAD vectors containing the E1 gene controlled by the human midkine promoter (Ad5F35/MKp-E1 and Ad5/MKp-E1, respectively) were constructed. Western blotting and cell viability assays were carried out in cells transfected with Ad5/MKp-E1 and Ad5F35/MKp-E1.
Coxsackie and adenovirus receptor (CAR), a cell surface target of Ad5, and CD46, a cell surface target of Ad35, were expressed in all the malignant mesothelioma cell lines examined here, as much as in HEK293 cells, with no significant differences in the expression levels among cells. Both Ad5/MKp-E1 and Ad5F35/MKp-E1 induced oncolysis of malignant mesothelioma cells in a viral particle-dependent manner, with similar efficacy.
The results of the present study suggest that both Ad5/MKp-E1 and Ad5F35/MKp-E1 are useful for the gene therapy of human malignant mesothelioma.
腺病毒载体已被用于癌症基因治疗。本研究考察了腺病毒 5 型（Ad5）和纤维替代条件复制腺病毒（CRAD）Ad5/F35 载体对人恶性间皮瘤细胞 MSTO-211H、NCI-H28、NCI-H2052 和 NCI-H2452 细胞的溶瘤作用。
对于腺病毒，第一个 mRNA/蛋白（感染后约 1 小时）是 E1A。构建了含有人中期因子启动子控制的 E1 基因的 Ad5F35 和 Ad5 CRAD 载体（分别为 Ad5F35/MKp-E1 和 Ad5/MKp-E1）。用 Ad5/MKp-E1 和 Ad5F35/MKp-E1 转染的细胞进行 Western blot 和细胞活力测定。
柯萨奇病毒和腺病毒受体（CAR），Ad5 的细胞表面靶标，和 CD46，Ad35 的细胞表面靶标，在所有检查的恶性间皮瘤细胞系中表达，与 HEK293 细胞一样，细胞之间的表达水平没有显著差异。Ad5/MKp-E1 和 Ad5F35/MKp-E1 均以病毒颗粒依赖性方式诱导恶性间皮瘤细胞的溶瘤作用，具有相似的疗效。
本研究结果表明，Ad5/MKp-E1 和 Ad5F35/MKp-E1 均可用于人类恶性间皮瘤的基因治疗。
