Inhibition of renal cancer cell growth by oncolytic adenovirus armed short hairpin RNA targeting hTERT gene

Abstract

RNA interference (RNAi) has been proved to be a powerful tool for gene knockdown purpose and holds a great promise for the treatment of cancer. Our previous study demonstrated that the reduction of hTERT expression by means of chemically synthesized siRNAs and shRNAs expressed from plasmid resulted in proliferation inhibition in human renal carcinoma cells. In this study, we constructed a novel oncolytic adenovirus-based shRNA expression system, ZD55-hTERT, and to explore ZD55- hTERT–mediated RNAi for hTERT gene silencing. Our results showed that ZD55-hTERT could induce silencing of hTERT gene effectively, allow for efficient tumor-specific viral replication and induce the apoptosis of tumor cells effectively in vitro and in nude mice. We conclude that combining shRNA gene therapy and oncolytic virotherapy can enhance antitumor efficacy as a result of synergism between CRAd oncolysis and shRNA antitumor responses.