Gene Therapy in Colon Cancer Cells with a Fiber-modified Adenovector Expressing the TRAIL Gene Driven by the hTERT Promoter

Abstract

Background: Repeated administration of adenoviral vectors can lead to cell resistance, probably because of the initial coxsackie-adenovirus receptor (CAR). Modified adenoviral vectors containing an Arg-Gly-Asp (RGD) sequence can overcome resistance. We constructed an adenoviral vector with RGD-modified fibers, expressing the TRAIL gene from the human telomerase reverse transcriptase (hTERT) promoter (designated Ad/TRAIL-F/RGD), and tested its antitumor activity in 5 colon carcinoma cell lines. Materials and Methods: Colon cancer cells were infected with Ad/CMV-GFP (vector control), Ad/gTRAIL (positive control) and Ad/TRAIL-F/RGD. PBS was used as a control. Cell viability was determined by proliferation assay. Cell-cycle analysis and quantification of Caspase-8 and TRAIL were used to identify apoptosis. Results: Treatment with Ad/TRAIL-F/RGD resulted in significantly less cell viability, increased Caspase-8 and TRAIL activity, and a greater apoptotic fraction than treatment with PBS or Ad/CMV-GFP. Conclusion: The adenoviral vector Ad/TRAIL-F/RGD could become a potent therapeutic agent for the treatment of colon carcinoma.