Beneficial oncolytic effect of fiber-substituted conditionally replicating adenovirus on human lung cancer

Adenovirus vectors have been utilized for a variety of cancer gene therapy. The present study examined the oncolytic effect of adenovirus type 5 (Ad5) and fiber-substituted conditionally replicating adenovirus (CRAD) Ad5/F35 vectors on human lung cancer A549 cells (an epithelial adenocarcinoma cell line), SBC-3 cells (a small-cell cancer cell line), and Lu-65 cells (a giant-cell lung cancer cell line).

For adenovirus, the first mRNA/protein to be made (~1 h after infection) is early region 1A (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. Reverse transcription-polymerase chain reaction (RT-PCR), western blotting and cell viability assays were carried out in cells transfected with Ad5/MKp-E1 and Ad5F35/MKp-E1.

Less expression of mRNA and protein for coxsackie and adenovirus receptor (CAR), a cell surface target of Ad5, was found with lung cancer cells as compared with the expression in human embryonic kidney 293 (HEK293) cells, but otherwise mRNA and CD46 protein, a cell surface target of Ad35, was expressed in lung cancer cells as much as in HEK293 cells. Both Ad5/MKp-E1 and Ad5F35/MKp-E1 induced oncolysis of lung cancer cells in a viral particle-dependent manner, with more efficient advantage for Ad5F35/MKp-E1.

The results of the present study suggest that Ad5F35/MKp-E1 is more useful for the gene therapy of human lung cancer than Ad5/MKp-E1 is.