Antitumor effects of a dual cancer-specific oncolytic adenovirus on colorectal cancer in vitro and in vivo.

The efficacy and specificity of treatment are major challenges for cancer gene therapy. Oncolytic virotherapy is an attractive drug delivery platform for cancer gene therapy. In the present study, the dual-specific antitumor oncolytic adenovirus, Ad-Apoptin-hTERT-E1a, was used to infect SW1116 human colorectal carcinoma (CRC) cell lines and CT26 mouse-CRC-cell bearing BALB/c mouse models for testing antitumor effects in vitro and in vivo. The in vitro assays revealed that infection with Ad-Apoptin-hTERT-E1a induced a significant cytotoxic effect on the CRC cell line, SW1116; however, the normal human cell line, GES, was only slightly inhibited by the recombinant adenovirus. Acridine orange and ethidium bromide staining and an annexin V assay indicated that infection of SW1116 cells with Ad-Apoptin-hTERT-E1a resulted in a significant induction of apoptosis. Furthermore, western blotting and flow cytometry revealed a decrease in the mitochondrial membrane potential (MMP), the release of cytochrome c and the activation of caspase 3, 6 and 7 in Ad-Apoptin-hTERT-E1a-infected SW1116 cells. In the animal models, Ad-Apoptin-hTERT-E1a was shown to significantly inhibit tumor growth and extend the survival times of the animals. Therefore, the experimental results indicated that Ad-Apoptin-hTERT-E1a has potential for application in tumor gene therapy.