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Increased vascular endothelial growth factor (VEGF) expression and tumor vascularization are correlated with both tumor progression and a poor clinical prognosis in colon cancer. There is increasing evidence that mda-7/IL-24 has potent growth suppression activity and induces apoptosis in many different tumor cells. We constructed a recombinant replication-deficient adenovirus carrying both an anti-VEGF hairpin ribozyme and human IL-24 (Ad-Rz/IL-24) with an internal ribosome entry site and tested its VEGF inhibition effect and antitumor activity. The results showed that Ad-Rz/IL-24 significantly inhibited VEGF expression and angiogenesis in vitro and in vivo. The proliferation rate of xenograft tumors treated with Ad-Rz/IL-24 was approximately 50% lower than the rate of the xenograft tumors treated with adenovirus carrying a single gene anti-VEGF hairpin ribozyme (Ad-Rz) or IL-24 (Ad-IL-24) alone. These findings demonstrated the potential therapeutic effect of this dual gene-expressing adenovirus for cancer gene therapy.

Antitumor activity of an adenovirus harboring two therapeutic genes, anti-VEGF ribozyme and human IL-24, in colon cancer